Psychotherapy Brown Bag

Manipulating memory: investigating morphine as a method of preventing PTSD

by Joye C. Anestis

The New York Times is really into providing topics for PBB lately.  Last night, I discovered the provocatively titled article "Morphine May Help Traumatic Stress."  We have spent a good amount of time here on PBB discussing PTSD in general, as well as the data on its treatment...and neither Mike nor I have ever come across an article promoting morphine as an effective treatment, so my curiosity was peaked.  Turns out, the Times was reporting on some preliminary data about morphine as a sort of "morning-after pill" for trauma (to use the words of journalist Benedict Carey) that would prevent the development of PTSD.  Prevention of PTSD is definitely an important national health goal (as is the prevention of any mental illness)...and the use of a pill to do so is intriguing.  I mean, just think of the implications if individuals brought into the hospital for trauma could be given a pill to reduce their risk of developing PTSD (for another treatment that purports to prevent PTSD, read about Critical Incident Stress Debriefing - this treatment has proven to be harmful for clients). After reading the Times summary of the study, and assuming that the findings were probably overstated (as research findings generally are in the media), I looked up the original article, published in the prestigious New England Journal of Medicine (looks like NEJM is currently offering free full text here).  

Apparently, an earlier study noted that morphine administration had protected children with burn injuries from developing PTSD (Saxe et al., 2001).  A few other studies offer some support for this practice in adults (e.g., Bryant et al., 2009).  The current authors (who are employed by the Naval Health Research Center), combed through the U.S. Navy-Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database (they abbreviate this: CTR EMED), a large database designed to document the records of casualties in the Iraq military theater during and after battle.  They looked at the use of morphine during early trauma care for injured military personnel.  Injured military personnel were identified as those brought to "forward medical treatment facilities" (the facilities closest to the point of injury) with injuries during Operation Iraqi Freedom (defined as the 36-month period from January 2004 through December 2006).  The Navy-Marine Corps CTR EMED contained information from "medical encounter forms" used at these facilities.  These forms include "demographic data, time of arrival at the facility, detailed information on the mechanism of injury, and comprehensive treatment data, including medications administered during early resuscitation and trauma care, dosages, route of administration, and interval between arrival at the facility and initiation of treatment" (p. 111).  Information was also available on the severity of injury.  PTSD diagnoses were obtained from the Career History Archival Medical and Personnel System and verified by reviewing medical records.  PTSD assessment were made 1-24 months from the date of injury and were based on DSM-IV criteria.

Of the 696 personnel, 243 developed PTSD and 453 did not.  90% of them had an Injury Severity Scale Score of 16 or less (the highest score on the scale is a 75).  The remaining 10% (i.e., > 16) were considered to have serious injuries.  There were no significant differences on the mechanism of injury between the PTSD and non-PTSD groups.  Morphine use was common in both groups of personnel.  Use of other meds with psychotropic effects was uncommon.  The authors used odds ratios to examine the association between morphine use and risk of PTSD.  An odds ratio is a measure of effect size which can be used to measure the strength of association between 2 binary variables.  The use of morphine directly after injury was significantly associated with a reduced risk of PTSD (odds ratio, 0.47; p < 0.001), and the significant association remained after adjusting for severity of injury.  Multivariate-adjusted odds ratios for the association between morphine use and reduced risk of PTSD, adjusting for demographic and clinical variables (age, injury severity, amputation status, mechanism of injury, mild traumatic brain injury), were also significant (odds ratio, 0. 49; p < 0.001).

Unlike the definitive conclusions drawn by the Times, the article's authors are cautious in discussing these findings - noting that morphine use in trauma care may be protective against subsequent PTSD.  The data they provide is preliminary, and several limitations prohibit any grand conclusions. In my opinion, the primary problem with this study is its observational nature.  Because they looked at morphine use and subsequent PTSD diagnosis retrospectively, the authors cannot say that morphine use caused a lower risk for PTSD.  A more rigorous study would have taken injured military personnel and randomly assigned them to morphine treatment or a no-morphine control group (although there are definite ethical considerations in doing this, including the provision of some equally effective, alternative pain management solution).

However, while we are a long way from firmly arguing for the use of morphine to prevent PTSD, the ideas behind its use in a preventative fashion are based on some really interesting theories.  One proposed mechanism of morphine's effectiveness is the relationship between morphine and memory.  It is proposed that such pharmacotherapy could "decrease or impede memory consolidation and the associated conditioned response to fear after a person goes through a traumatic event" (Holbrook et al., p. 111).  So, one potential route of effectiveness is that morphine would prevent traumatic memories from being formed, or at least decrease the intensity of the memory so that it would not be as fearsome.  Another contributing idea is that a reduction in perceived pain levels may lower risk.  This idea is based on some studies which have found that self-reported pain levels immediately after serious injury were significantly associated with risk for PTSD (Bryant et al., 2009; Norman et al., 2008; Zatzick & Galea, 2007).  It seems that the more painful an experience is perceived, the more likely PTSD is as an outcome...by manipulating pain perception, this risk is decreased.  I would love to hear your thoughts on these 2 proposed mechanisms of action.  I personally find them compelling and fascinating,but don't have the expertise to speak to them with any confidence.  Anyone out there with some expertise in memory development want to chime in?  What about potential costs vs. benefits of memory alteration as a treatment?  Any thoughts on the pain perception theory?  I'm looking forward to your thoughts!

Joye Anestis is a doctoral candidate in clinical psychology at Florida State University.

Antidepressant medications versus placebos: The impact of depression severity

by Michael D. Anestis, M.S.

In a number of past PBB articles, we have discussed the mountains of research supporting the efficacy and effectiveness of antidepressant medications in the treatment of depression.  Within the past 24 hours, both Thomas Joiner and Jed Siev have alerted me to an article published in the most recent issue of the Journal of the American Medical Association (JAMA) that provides some valuable insights capable of adding a lot to this conversation.  I appreciate their heads up on this and think that it would be useful to talk about this paper today.  For those interested in reading another take on the findings, the study was also discussed in today's New York Times.

The authors - and there are a lot of them - were Jay Fournier, Robert DeRubeis, Steven Hollon, Sona Dimidjian, Jay Amsterdam, Richard Shelton, and Jan Fawcett (2010).  These researchers represent some of the most prolific in the field and we have covered various examples of their work numerous times over the past year (type in their names in the Lijit search box at the top of the page for examples). In this particular study, the authors wanted to examine a question with enormous clinical implications: does the severity of an individual's depression impact the utility of antidepressant medication relative to a placebo.

There were several motivating forces that drove the authors to pursue this particular series of analyses.  First of all, prior work has, in fact, supported the notion that the degree to which antidepressants outperform placebos increases as the severity of depression increases (e.g., Kirsch et al., 2008; Kahn et al, 2002).  Importantly, in the Kirsch et al. (2008) study, the authors noted that, in order for antidepressants to result in a clinically significant difference in utility over placebos, individuals typically needed to score at least 28 on the Hamilton Depression Rating Scale (Hamilton, 1960). As a point of reference, scores of 18 or lower are considered to represent mild to moderate depression, scores of 19 to 22 represent severe depression, and scores of 23 or greater represent very severe depression (APA, 2000). So, the authors noted that prior work had indicated that, in order for antidepressants to have an impact above and beyond what could be accounted for by placebo, individuals needed to be very severely depressed.  At the same time, the authors noted that these earlier findings included some fairly substantial limitations.

The limitations of the prior studies tie into another motivating force behind this study.  Earlier trials like the ones mentioned above typically require that participants be severely depressed.  There is nothing inherently wrong with looking at the treatment of severely depressed individuals; however, such individuals make up only a small minority of those who present for the treatment of depression.  In other words, mildly or moderately depressed individuals who are prescribed antidepressants are essentially done so on the basis of studies that look only at the impact of antidepressants on people whose condition is much worse than their own rather than research demonstrating that antidepressants offer clear benefits for individuals at their particular level of symptomatology. Additionally, many clinical trials involve what is referred to as a placebo washout period.  This procedure involves giving a placebo to a participant for a period ranging from a couple days to two weeks without letting them know it is a placebo and then eliminating from the analyses prior to randomization any participant who demonstrates marked improvement in depression during this period. In other words, this procedure involves eliminating participants who respond to placebo and including those who do not, thereby likely artificially inflating the difference between those who receive medications and those who receive placebo (as those who respond well to the placebo during the washout period are not included in the analyses). 

One final limitation of earlier trials that is important to consider relates to a point we have raised before on PBB: the limitations of meta-analysis.  Generally speaking, in a meta-analysis, a number of studies are combined and their results are averaged in order to find overall effects.  In doing this, a study that includes 100 people and a study that includes 400 people are simply combined to represent 2 studies (and so on depending upon how many studies are included in the meta-analysis) so, rather than a sample of 500 people on whom we can run sophisticated analyses, we have a tiny sample size of two.  Additionally, because most studies use different outcome variables, outcomes are combined arbitrarily and weighted equally, thus completely altering and misstating what was actually found in the original studies.

So...what did Fournier and his colleagues (2010) do about this?  First, they found randomly controlled trials of FDA-approved antidepressant medications in the treatment of a wide range of depression severity.  In other words, they did not only look at severely depressed individuals.  All of the studies included had to involve a comparison of antidepressant medication and placebo that lasted at least 6 weeks.  No studies that involved placebo washout periods were included.  Additionally, all of the studies had to use the Hamilton Depression Rating Scale, thereby ensuring that the authors would not be comparing different outcomes to one another as though they were the same.  The final - and perhaps most important - inclusion criterion was that, in order to be included, the authors had to be granted access to the original data, thereby allowing them to analyze all of the participants rather than simply looking at the aggregate results.  Because of this, the authors were able to combine the samples of all of the included studies (a total of 6 studies), resulting in a total of 718 participants (434 in the antidepressant condition and 284 in the placebo condition).  Three of the studies included in the analyses examined Paxil, which is a selective serotonin reuptake inhibitor and three of the studies examined imipramine, which is a tricyclic antidepressant.  All of the participants were at least 18 years of age and the authors found that attrition rates did not differ between conditions, meaning that participants were no more likely to drop-out of the placebo condition than the antidepressant condition and vice versa.

After combining the samples from the six studies, the authors ran their analyses and found that, as expected, the degree to which antidepressants outperformed placebos depended upon how depressed the individual was at baseline.  For mild to moderate depression, the effect size, which is a measure of how powerful a finding is, was very small (d = .11).  For severe depression, the effect size again was very small (d = .17).  For very severe depression, however, the effect size (d = .47) was approximately "moderate" using the standard established by Cohen (1988). Taking this a step further, the authors found that, to meet the least stringent criterion for clinical significance established by the National Institute for Clinical Excellence (NICE) of the National Health Service in England, individuals needed to score at least a 25 on the Hamilton Depression Rating Scale in order for antidepressants to have an impact above and beyond a placebo.  Using stricter criteria, the requirement increased to 27.  Keep in mind that many depressed individuals score well below that number and that a score of 23 is said to represent very severe depression. 

In order to make sure that very mild cases were not obscuring the findings, the authors re-ran their analyses while only including the five studies examining major depression (the other study looked at minor depression).  The results were unchanged.

In order to ensure that participant drop-out did not artificially impact the findings, the authors re-ran their analyses while only including individuals who completed the entire study.  This resulted in only a minor change in the results, with the minimum required score dropping from 25 to 24.

So what does this study tell us? First of all, it raises questions regarding the utility of antidepressants in the treatment of mild to severe depression.  Secondly, it highlights the importance of running similar studies while including various forms of psychotherapy, thereby allowing a measure of the degree to which empirically supported treatments for depression, such as cognitive behavioral therapy and interpersonal psychotherapy, impact these less severe presentations.

As is the case with most of the studies we discuss on PBB, this work again shines a light on the importance of understanding how doctors and scientists arrive at their conclusions rather than simply listening to what those conclusions are. If we do not develop an understanding of how people determine whether or not a particular treatment works, we will be unable to know when findings are overstated or data is misinterpreted.

Please keep in mind that this article is not meant as an attack on antidepressant medication.  A quick read of our prior articles on this topic will reveal that we are very much in favor of the use of any empirically supported treatment for a particular diagnosis, whether that treatment is a form of psychotherapy or a form of pharmacotherapy.  That being said, this article is most definitely intended as a bit of a wake-up call, as sometimes the data give us a more complicated picture than we anticipated seeing.

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If you would like to learn more about depression and its treatment, we recommend the following items, each of which is available through our online store for scientifically-based psychological resources:

• Cognitive Therapy of Depression by Aaron Beck, John Rush, Brian Shaw, and Gary Emery
  

• Treatment Plans and Interventions for Depression and Anxiety Disorders by Robert Leahy and Stephen Holland

• Feeling Good: The New Mood Therapy Revised and Updated by David Burns

• The Feeling Good Handbook by David Burns

Mike Anestis is a doctoral candidate in the clinical psychology department at Florida State University

Utilization of depression treatment: Demand is high but access is low

by Joye C. Anestis

We have spent a considerable amount of time here at PBB discussing the treatment of major depression.  If you're a regular reader, you know that effective depression treatments are well-documented, and consumers have a variety of choices when seeking out evidence-based treatments (current ESTs for depression are cognitive-behavioral therapy, CBASP, interpersonal psychotherapy, and antidepressants).  Despite the success in treating depression, only a handful of depressed individuals actually receive help (Kessler et al., 2003; Young et al., 2001).  This issue is at the heart of PBB, where we try to raise public awareness of the effective treatments available in an effort to help end some suffering. 

A new study in Archives of General Psychiatry aimed to further understand the overall underutilization of depression treatment in two ways: separating treatment into either pharmacotherapy and psychotherapy (previous studies have only looked at treatments lumped together into one group) and examining underutilization in specific racial/ethnic groups.  The authors, Hector Gonzalez and colleagues, utilized the National Institute of Mental Health Collaborative Psychiatric Epidemiology Surveys for their investigation.  This database consists on noninstitutionalized individuals who were administered the World Mental Health Composite International Diagnostic Interview.  Among the information gleaned from this interview is a 12-month diagnosis of major depressive episode.  The authors were able to examine 5 ethnic/racial groups within this database: Mexican, Puerto Rican, Caribbean black, African American, and non-Latino white (race/ethnicity was self-identified).  As mentioned before, the authors looked at two depression care outcomes: pharmacotherapy (determined by self-report and pill bottle inventories) and psychotherapy (self-report). 

An interesting aspect of this study was the authors' investigation of the adequacy of treatment.  Following the American Psychiatric Association's Practice Guideline for the Treatment of Patients with Major Depressive Disorder (2000), adequate pharmacotherapy use was defined as antidepressant use for at least 60 days with supervision by a prescribing clinician for at least 4 visits in the past year.  Adequate psychotherapy was operationalized as at least 4 visits to a mental health professional in the past year lasting on average for at least 30 minutes (I don't know about you but that seems like a very generous definition of adequate therapy!).  It is important to point out here that the authors did not further specify depression treatment (i.e., all psychotherapies were lumped together) and so were unable to examine use of ESTs versus other treatments.

Still the results are telling about the state of mental health care in the United States, and especially the racial/ethnic disparities that exist.  Of those meeting 12-month major depressive episode criteria, only 50.76% (standard error = 2.76) received any depression therapy and only 21.28% (standard error = 1.60) received adequate depression treatment!  I find this result completely tragic...only about half of the depressed people in this country received any kind of treatment and a little more than a fifth received "adequate" care based on, in my opinion, a very generous definition (for psychotherapy, at least 4 visits of at least 30 minutes in length)! 

Furthermore, while none of the 5 racial/ethnic groups examined differed significantly in the overall severity of depression, marked differences in treatment use did emerge.  Specifically, African Americans and Mexican Americans were the least likely to receive depression care, especially adequate care. Pharmacotherapy use overall and adequate pharmacotherapy treatment was lowest for Mexican American, Caribbean black, and African American individuals.  While overall psychotherapy use was higher than pharmacotherapy use, again Mexican American, Caribbean black, and African American individuals reported the lowest use.  Interestingly, the rate of adequate treatment was higher for psychotherapy than pharmacotherapy.  In terms of depression prevalence, Puerto Rican individuals had the highest 12 month major depression prevalence, a finding consistent with previous studies (Alegria et al., 2007; Vega et al., 2009), but these individuals had treatment rates consistent with (and sometimes higher than) non-Latino whites.  The authors reported some interesting conclusions about health insurance coverage, an important factor they argued could contribute greatly to ethnic/racial minority groups having access to mental health care.  They found that health insurance coverage was associated with higher depression care but not with adequate care...so health insurance does increase access to care but, contrary to what I would expect and hope, it does not ensure better care.  Importantly, a lack of health insurance coverage partially explained the depression care disparities for Mexican American individuals but not for African American individuals, meaning that other factors influence access to care in for this population.  Other factors that have been suggested, but not investigated in this study, include perceived discrimination and a perception of bias in the health care system.

Over the past few decades, there has been a strong movement within clinical psychology to change the image of mental health treatment away from something just done by rich, White people (this stereotype was perpetuated during the heyday of Freudian psychoanalysis when only a small number of people could afford the years-long treatment advocated).  Many people are working to increase access to mental health care to all individuals in need.  The findings reported here by Gonzalez and colleagues indicate that there is still much work to be done, not only with ethnic/racial minority groups (and especially African Americans and Mexican Americans), but with the population as a whole.  Effective (and often fast-acting) treatments exist...we've just got to let the world know about them!

Joye Anestis is a doctoral candidate in clinical psychology at Florida State University.

Is it going to come back?: Relapse rates after CBT and/or antidepressant treatment in major depression

by Joye C. Anestis

***Thanks to a thoughtful thread on the ABCT listserv for inspiring this post and leading me to this article.***

An important and thoughtful question often posed by clients who are experiencing some symptom relief from treatment is "what is the likelihood that my mental illness will recur?"  Just as, say, a cancer patient would want to the know the odds of relapse, so do those being treated for mental illness.  The answer to this question can be complicated, as it not only depends on which mental illness you're dealing with but also, importantly, what treatment you received.  There is ample evidence that relapse rates differ between treatments.  The fact of treatment-influenced relapse rates is another important consideration when presenting therapies to clients...seems only logical to consider using the most effective treatment available with the most hopeful relapse data.

For today, I'm only going to focus on major depression.  In 2007, Vittengl, Clark, Dunn, & Jarrett conducted a meta-analysis of studies examining the relapse-recurrence rates in cognitive-behavioral therapy (CBT) for major depression (if you are unfamiliar with meta-analysis, click here for a review).  These authors were interested in answering 4 questions (the questions are delineated below).  28 total studies met their inclusion criteria (see the article for details on what these were) and were included in the review.

How common is relapse-recurrence in those who respond to acute-phase CBT (CBT applied during a major depressive episode with the goal reducing depressive symptoms and producing remission)?

• Importantly, an acute treatment is discontinued when goals are met after a certain number of sessions (e.g., 12)...so this data refers to short-term treatment.  13 studies contained data to answer this question.  The mean proportion of relapse across these studies was 39% over a mean of 74 weeks.  The relapse rate for individual studies varied greatly, suggesting that some other variable could be influencing these findings.  The authors identified 7 possible moderators.  For the studies that had higher relapse rates, the following factors moderated outcome: longer follow-up periods, use of relapse-recurrence rates from survival analysis instead of simple proportions, assessment of therapist competence, and use of major depression diagnostic criteria in relapse-recurrence definitions.  Studies with lower relapse rates reported assessment of therapist adherence, left gaps in time in the follow-up assessment, and utilized a cutpoint in a depression measure in their relapse-recurrence definition.  Unfortunately, actual interpretation of any of these moderators is difficult, as they are most likely highly inter-related.

Does acute-phase CBT reduce relapse-recurrence more than other acute-phase treatments?

• Acute-phase CBT vs. acute-phase pharmacotherapy (7 studies): Again, remember that an acute treatment is discontinued after a short period of time.  CBT significantly reduced relapse-recurrence compared with pharmacotherapy.  In fact, a patient treated with CBT has a 61% chance of a better outcome (no relapse) than one treated with pharmacotherapy.  Over a mean of 68 weeks, the relapse rate of CBT 39% and the relapse of pharmacotherapy was 61%.
• Acute-phase CBT + pharmacotherapy  vs. acute-phase pharmacotherapy alone (6 studies): Again, the inclusion of CBT is superior.  Over a mean of 56 weeks, CBT + pharmacotherapy yielded relapse rates of 38%, whereas the relapse rates for pharmacotherapy alone were 65%.  Patients who received the combination treatment had a 61% chance of a better outcome than those treated with pharmacotherapy alone.
• Acute-phase CBT + pharmacotherapy vs. acute-phase CBT alone (3 studies - due to the small number of studies, these findings should be viewed with caution):  Adding medication to CBT did not reduce the relapse rate significantly when compared to CBT alone.  Over a mean of 61 weeks, relapse-recurrence rates were 33% for CBT alone and 39% for the combination.
• Acute-phase CBT vs. other acute-phase depression-specific psychotherapies (4 studies - again, due to the small number of studies, these findings should be viewed with caution):  Relapse rates did not differ significantly between CBT and other depression-specific psychotherapies, as a whole.  Looking at the specific therapies, 2 of the 4 studies compared CBT to other behavioral interventions, one compared CBT to interpersonal psychotherapy, and the only study to show a significant difference (lower relapse rate for CBT) used a psychodynamic-interpersonal therapy.

Does continuation-phase CBT (CBT applied to prolong remission and reduce the likelihood of relapse-recurrence...essentially booster sessions of CBT) reduce relapse-recurrence more than nonactive control conditions?

• Relapse rates at the end of continuation CBT (4 studies): Continuation CBT significantly reduces relapse rate compared to non-active control conditions.  Averaging over 41 weeks, continuation CBT had a relapse rate of 12% and the nonactive control condition had a relapse rate of 38%.
• Relapse rates after discontinuing continuation CBT (5 studies):  Here again, continuation CBT is important, significantly reducing relapse rates compared to nonactive controls.  Over an average of 153 weeks, the relapse rate of continuation CBT was 40%, compared to the 73% relapse rate for nonactive controls.

Does continuation-phase CBT reduce relapse-recurrence more than other active treatments?

• Relapse rates at the end of continuation treatment (5 studies):  The difference was non-significant (p < .06); however, the relapse rate of CBT was 10%, compared to a 22% relapse rate for active controls, over a mean of 27 weeks.
• Relapse rates after discontinuing continuation treatment (8 studies): Here, continuation CBT reduced relapse significantly.  Over a mean of 114 weeks, the relapse rate of CBT was 42% and the relapse rate for active controls was 61%.

So, relapse is common in any treatment for depression, but the rates are significantly lower for CBT than for medication...and providing booster sessions of CBT after acute treatment serves to further decrease the relapse rates.  The authors interestingly place these findings in a public health perspective (I personally love it when researchers do this, because I find it really drives the point home)...so here's what these findings really mean:

• Based on current epidemiological data, approximately 35,000,000 people have major depression each year in the U.S. (Kessler et al., 2003)...
• And approximately 16% (5,600,000) of depressed folks receive adequate pharmacotherapy (Young et al., 2001)
• Furthermore, approximately 50% (2,800,000) of patients with depression respond to acute-phase treatment (Hollon et al., 2005) and
• Approximately 72% (2,016,000) of patients discontinue pharmacotherapy within 90 days (Olfson et al., 2006).
• Then the potential savings of treating these folks with acute phase CBT is about 448,000 relapses annually!

Considering the cost (both time and money) of long-term pharmacotherapy and the lack of desire in patients to take medication in the long-term, acute CBT with booster sessions seems the best way to combat relapse.

Joye Anestis is a doctoral candidate in clinical psychology at Florida State University.

The relationship between antiepileptic drugs and suicide attempts in bipolar disorder

by Joye C. Anestis

Ok, prepare yourself for this one...the article was hard for me to get through, making it even harder to translate into non-scientific jargon.  Medical journals, as opposed to psychology journals, like to make things difficult. 

Bipolar disorder is a difficult illness to live with.  Among the many difficulties faced by those with this illness is usually a lifetime of medication management.  Psychotherapy has been shown to be a useful adjunct to pharmacotherapy, but pharmacological treatment is considered the front-line for bipolar disorder. The most common is lithium, but some alternative medications have been identified as useful in managing bipolar disorder.  Specifically, antiepileptic medications are commonly prescribed (on a side note, antiepileptic meds are also commonly prescribed for borderline personality disorder).  As you can guess from their name, this class of drugs was originally developed to control seizures in individuals with epilepsy but they also have mood stabilizing effects. 

Recently, the Food & Drug Administration (FDA) has questioned the safety of these drugs in regard to suicidality.  They conducted a meta-analysis of placebo-controlled trials of 11 antiepileptic drugs (AEDs)  - importantly, this meta-analysis examined AED use for any reason, not just psychiatric ones.  Results revealed that 0.43% of those treated with AEDs reported suicidal behavior or ideation compared to 0.22% of patients in placebo groups.  On January 31, 2008, the FDA issued an alert to healthcare providers about an increase risk for suicidal behavior and ideation with AEDs, and on July 10, 2008, the FDA's scientific advisory committee voted that there was a significant association between suicide and AEDs but voted against a black box warning similar to the one found on antidepressant labels(click here for the FDAs webpage on this topic).

Obviously, increased risk of suicide is always concerning, especially when the risk concerns a population already at elevated risk of suicidality.  Without treatment, an estimated 10 per 1000 individuals with bipolar disorder complete suicide annually and 40 per 1000 attempt suicide (Baldessarini et al., 2006).  Risk of completed suicide and suicide attempt in bipolar disorder are 100-fold and 10-fold higher, respectively, than the risk of the general population.  So it's important to determine if AEDs specifically affect suicide risk in bipolar disorder...it would be troubling to discover that the primary treatment for an illness made those taking it less safe! 

A new study by Gibbons, Hur, Brown, & Mann (2009) in Archives of General Psychiatry investigated this very topic and attempted to correct some of the methodological problems found in the FDAs study and other studies on this topic.  Gibbons et al. obtained data from a large database of longitudinal medical claims data, representing over 47 million people.  All individuals with a diagnosis of bipolar disorder who were enrolled in the same healthcare plan for 1 year before and after the index diagnosis data were included  (i.e., they included everyone with the diagnoses continuous data pre- and post-treatment data).  47,918 patient met these criteria, and 1,226 of them had at least one suicide attempt.  Analyses were restricted to AED monotherapy, which they defined as taking only 1 of the 11 AEDs in the year following diagnosis and not taking lithium.  Other psychiatric medications were included as covariates in the analyses, including concomitant antidepressant, other antiepileptic, antipsychotic use or lithium monotherapy - meaning they could statistically remove the effects from these other treatments in order to examine findings for just the AEDs.  For comparison groups, the researchers identified a group of patients who received none of the 11 AEDs or lithium in the year following diagnosis and a group of patients who received no central nervous system (CNS) medication.

Interestingly, the results explicitly contradict the FDA warnings.  Gibbons et al. did a lot of complicated analyses, and I've reported just the primary ones below.  Please refer back to the original article for more details.  But overall they found:

• After treatment, there was no significant difference in suicide attempt rates for those treated with an AED and those received no AED or lithium.
• When each individual AED was examined, similar findings appeared with 2 exceptions, topiramate and carbamazepine, which had significantly greater post-treatment risk than no treatment.
• A small but significant increase was found with lithium compared with no treatment.  Overall, AEDs were associated with lower suicide attempts than lithium.
• When they did within-subjects comparisons, rate of suicide attempt was significantly greater prior to any AED treatment than after.  Similar reductions were found for the individual AEDs and lithium, except for topiramate and carbamazepine.  Also, interestingly, the pretreatment suicide attempt rate was significantly higher for the group that ultimately received an AED than the no-treatment suicide attempt rate, indicating the the AED group was potentially more impaired prior to treatment.
• Suicide attempt rate for patients not treated with any CNS drug was significantly higher than those who received an AED only.
• Sensitivity analyses revealed that these effects were maintained for the duration of treatment.  They were also found when looking at single attempters and multiple attempters.

So, in sum, it appears that AEDs are not associated with increased suicide attempt risk in folks with bipolar disorder.  Certainly, a number of limitations exist in the present study, including the use of medical claims data which likely underreport suicide attempts, no information on completed suicides (just attempts), no data on intensity of treatment, lack of random assignment to treatment, reliance on diagnoses from the database and not from structured interviews, no consideration of treatment adherence, and the fact that patients could have had a concomitant illness (such as epilepsy) for which the AED was prescribed.  Despite all of this, it is remarkable that the AED group had such higher rates of suicide attempts prior to treatment and still achieved lower rates post-treatment, compared to the control groups.  Hopefully, the FDA will consider these findings, and any future data that may emerge on this topic, as they issue warnings.  

For more information on suicide and bipolar disorder, check out our online bookstore.

Joye Anestis is a doctoral candidate in clinical psychology at Florida State University.

Black box warning: Clarifying the connection between antidepressant use and suicide

by Michael D. Anestis, M.S.

Given our recent articles on the various psychosocial and pharmacological treatments for depression (see here and here), I thought it would be a worthwhile venture to open a conversation on the link between antidepressant use and suicidality.   To do this, I would like to summarize a recent article published in Professional Psychology: Research and Practice by David Rudd, Liliana Cordero, and Craig Bryan (author of the April 2009 PBB featured article).  In this article, the authors sought to clarify the actual meaning of the black box warning on antidepressants and to provide some preliminary data on shifts in suicide rates since the black box first appeared.

The Food and Drug Administration (FDA) first issued the black box warning for antidepressants in 2004, declaring that children and adolescents utilizing antidepressants were at an increased risk for "suicidal thinking and behaviors."  In 2007, the warning was expanded to include young adults up to the age of 24.  Quite understandably, this raised significant concern amongst clinicians, researchers, and the general public.  The idea of a popular treatment for the most common mental illness contributing to suicidality in children and adults is horrifying.  That being said, the vast majority of who have heard about this warning - whether they are professionals or nonprofessionals in need of help - do not accurately understand what the black box actually tells us.

Before getting any further into this topic, I want to call your attention to a link provided in the article by Rudd, Cordero, and Bryan (2009).  Click on this link to read the complete FDA warning label and a supplemental medication guide for health care providers, patients, and family members.  

Now that you have access to the warning label itself, let's discuss what it actually tells us.  Based on a sample of 4,400 pediatric patients, the FDA felt compelled to warn about clinical worsening, particular with respect to the first months of an antidepressant drug prescription.  Additionally, the FDA suggested that, during this initial phase of treatment, clients should have more frequent contact with practitioners and suicide risk should be assessed regularly.  What the warning does not do, however, is mention an increased risk for death by suicide.  Why not?  Because there was not a single death by suicide in the entire pediatric sample.  There was a statistically significant increase in suicidality - defined by the FDA in their study as thoughts of suicide and suicidal behaviors (e.g., failed attempts) - but there was no actual death by suicide.  As we have covered repeatedly in our articles on Joiner's (2005) interpersonal-psychological theory of suicidal behavior, there is a very real distinction between thoughts of suicide and suicide attempts and, additionally, there is a big difference between serious and non-serious attempts.  All of these thoughts and behaviors are troubling, but they are not all the same thing.

To clarify this point further, the FDA data indicated that, for individuals under the age of 18 who were prescribed antidepressants, there was an additional 14 cases of suicidality per 100,000 people relative to individuals prescribed a placebo.  For individuals between the ages of 18 and 24 who were prescribed antidepressants, there was an increase of 5 cases of suicidality per 100,000 people relative to individuals prescribed a placebo.  These are meaningful numbers, but remember, suicidality in this study did not involve death by suicide.  The suicidality rate in the antidepressant group was 4%, meaning 176 individuals exhibited suicidality.  By comparison, there was a suicidality rate of 2% in the placebo group, meaning 88 individuals exhibited suicidality.  A difference of 2% is not trivial, but it does indicate that results from 88 individuals (the difference between the two groups) resulted in a warning for all antidepressants.

Importantly, although there were deaths by suicide in the adult sample, there was no statistically significant difference in rates of suicidality between those on antidepressants and those taking a placebo pill for individuals between the ages of 25 and 64.  Additionally, for individuals over the age of 65 - the demographic with the highest global rate of death by suicide - there was a significant decrease in suicidality for individuals taking antidepressants (6 fewer cases per 100,000 people).  

When the FDA issued this warning, it was not their intention to imply that children and adolescents were dying by suicide as a result of using antidepressants.  Similarly, they did not want to discourage practitioners from prescribing antidepressants to these or any other age groups.  They simply wanted to call attention to a trend indicating deterioration during early months of therapy and to encourage increased contact between clients and practitioners during this period so as to facilitate regular risk assessments. The impact of the warning, however, has not mirrored the FDA's intentions.

Several studies have reported a substantial drop in the rates of antidepressant prescriptions.  In fact, Lineberry et al (2007) reported a 20% decrease in antidepressant prescriptions to children and adolescents.  Some might argue that this is fine, as it might mean that alternative paths towards health are being taken.  This, however, simply is not the case.  Libby and colleagues (2007) reported that there has been a significant drop in the number of children and adolescents being diagnosed with depression.  After the 2004 warning, depression diagnoses in this age group decreased by nearly 70%.  This does not mean fewer people meet criteria for depression, but rather that fewer people are actually being given the diagnosis.  Additionally, despite the decrease in antidepressant prescriptions, there has been no increase in the rate of individuals utilizing psychotherapy.  In other words, clinicians have responded to the black box warning by becoming less willing to diagnose depression and the general public has become less willing to seek help.  As such, we are not seeing anything resembling an increase in effective care.

Perhaps the most notable change since the institution of the black box warning on antidepressants has been an increased rate of suicide amongst the targets of the warning.  In the Netherlands, the youth suicide rate increased by 49% following the introduction of the warning label (Gibbons et al., 2007).  In the United States, there was an 18% increase in suicide rates for children, adolescents, and young adults (Bridge, Greenhouse, Weldon, Campo, & Kelleher, 2008).  In Canada, the child and adolescent suicide rate increased from 4 per 100,000 to 15 per 100,000 after the warning was issued.  This is not to say that the FDA is responsible for the increases, but rather that the warning has actually had the opposite of its intended effect, in large part because most individuals do not actually understand what it is saying.

The confusion regarding the black box warning also appears to be impacting adult populations.  Rudd, Cordero, and Bryan (2009) noted that several studies have found a decrease in antidepressant prescriptions for adults, despite the fact that the FDA study showed no relationship between suicidality and antidepressants for adults between the ages of 25 and 64 and a decreased suicidality rate for adults over the age of 65 who were prescribed antidepressants.  In other words, because of the findings for children and adolescents, clinicians appear to be less willing to prescribe helpful medication for adults and adults seem less willing to seek out effective care (Valuck et al., 2007).  Again, this would be less troubling if adults were increasingly seeking effective psychosocial care; however, there has been no such increase in psychotherapy usage.  This particular finding should be taken with a grain of salt, however, given that other studies have shown a massive increase in overall antidepressant usage.

Unfortunately, the black box warning has also failed to cause the desired increase in client contact, as fewer than 5% of patients meet the FDA suggestions for contact with practitioners, a rate that is identical to pre-warning levels.  Additionally, Cordero, Rudd, Bryan, and Corso (2008) found that, in a sample of prescribing practitioners, 91% misunderstood the black box warning and the vast majority believed that the data indicated an increased risk for death by suicide.

All of these findings taken together seem to indicate that, despite the best of intentions, the FDA's black box warning has not been helpful.  Many individuals mistakenly believe that antidepressants result in an increased risk of death by suicide, fewer clinicians are diagnosing individuals with depression, and fewer depressed individuals are seeking help.  Additionally, rather than decreasing, suicide rates in the target populations appear to have increased.  Ideally, greater clarity will be found through enhanced education, with practitioners and the general public choosing to read about the actual findings and researchers making a stronger effort to effectively publicize accurate information.

If you would like to learn more about this or other mental health topics, we encourage you to consult our online store.

Mike Anestis is a doctoral candidate in the clinical psychology department at Florida State University.

Predicting who will respond to a particular treatment for depression

by Michael D. Anestis, M.S.

Recently, I wrote an article in which I described the evidence that variations of cognitive-behavioral therapy and interpersonal psychotherapy perform as well as or better than antidepressant medication in the treatment of depression.  In the most recent issue of the Journal of Consulting and Clinical Psychology, Jay Fournier and colleagues (2009) published a study that elevated this conversation to another level.  In this particular study, the authors expanded upon the question of "which approach to treatment is more successful in reducing symptoms of depression" by asking "which individuals are most likely to respond to treatment and, of those, who will respond better to which treatment?"  These types of questions - those that allow us to better understand who the best candidates are for particular types of therapy - are pivotal targets for research if we are to develop an effective system of mental health care that adequately treats the broadest possible spectrum of individuals.

As an empiricist, I am very much in favor of comparative treatment research - studies that systematically test whether one therapeutic approach outperforms another in the treatment of a particular mental illness.  Such studies allow us to develop a hierarchy of treatments based upon objective results, thereby increasing our ability to quickly treat individuals presenting with mental illness.  This is, in fact, the basis for the empirically supported treatment (EST) movement.  At the same time, it is important to acknowledge that some individuals simply will not respond to the best available treatment.  Similarly, for mental illnesses such as depression for which there are several ESTs, none of which stands out as definitively superior to the others, clinicians are left without a clear guideline with respect to determining the best approach for a particular individual. 

Here is where research like the Fournier et al. (2009) study is so valuable.  The authors conducted a randomized controlled study examining individual responses to antidepressant medication and cognitive therapy for moderate to severe depression.  The sample was comprised of individuals seeking outpatient care for depression and included 60 individuals randomly assigned to receive cognitive therapy and 120 individuals randomly assigned to receive antidepressant treatment, with treatment lasting 16 weeks.

The first question the authors sought to answer was which variables predicted whether an individual was likely to respond to either treatment.  In other words, the authors were not examining which treatment performed better, but rather, which individuals were likely to show the expected benefits of treatment and which individuals were likely not to respond.  Their results indicated that individuals with a history of chronic depression, individuals who were older, and individuals with lower levels of intelligence were less likely to respond to cognitive therapy or antidepressants.  Importantly, this does not mean that such individuals are doomed to a poor response to either of these treatments.  It simply means that, on average, such individuals are less likely to respond.  In fact, other reviews have found that neither age nor intelligence significantly predicted depression treatment outcome (e.g., Dunkin et al., 2000; Hirschfeld, et al., 1998; Petersen, et al., 2002) As Fournier and colleagues (2009) suggest, this finding means that such individuals might be ideal targets for alternative treatment approaches.  Such approaches could include simultaneous cognitive therapy and antidepressant use, interpersonal psychotherapy, or an alternative approach with less empirical support.

The second question the authors sought to answer was which individuals were more likely to respond to cognitive therapy versus antidepressants.  In other words, the authors wanted to see whether particular characteristics of individuals could help predict the likelihood that they would exhibit a positive response to a specific treatment.  Here again, the data offered some interesting insights.  Individuals who were married or cohabiting, unemployed, or had experienced a significant number of recent negative life events (e.g., fired from a job, financial crisis, breakup from a relationship) were more likely to respond well to cognitive therapy than to antidepressants.  Here again, some caution is required in interpreting the results.  The fact that married individuals fair better in cognitive therapy does not mean that unmarried individuals or individuals not cohabiting fair better with antidepressants.  The results indicated that unmarried individuals and individuals not cohabiting were equally likely to benefit from one treatment versus the other.  The same thing goes for employment status and the number of recent negative life events.  Additionally, being married does not guarantee a positive response to cognitive therapy or a negative response to antidepressants.  It simply adjust the odds of responding to one treatment versus another. 

It is extremely important that we keep in mind that this is simply one study.  In order to have complete confidence that a particular variable (e.g., marital status) will impact an individual's response to a particular treatment, the same finding must be reliably and independently replicated by other research teams.  As the authors themselves noted, the work of Fournier and colleagues (2009) thus serves as a wonderful foundation for future work, not the final conclusion for a long-standing debate.  Hopefully other researchers will conduct equally well designed studies on this topic in the near future and offer us more insight into which individuals respond well to front line treatments for depression and, of those who do, which individuals are best served by which empirically supported treatments.

If you would like to learn more about empirically supported treatments for depression, we recommend the following resources, all of which are available through our online store:

• Cognitive Therapy of Depression - by Aaron Beck, M.D.

• Cognitive Therapy Techniques: A Practitioner's Guide - by Robert Leahy, Ph.D.

• Treatment Plans and Interventions for Depression and Anxiety Disorders - by Robert Leahy, Ph.D.

• Practicing Cognitive Therapy: A Guide to Interventions (New Directions in Cognitive-Behavior Therapy) - by Robert Leahy, Ph.D.

• Roadblocks in Cognitive-Behavioral Therapy: Transforming Challenges into Opportunities for Change - by Robert Leahy, Ph.D.
  

• Clinician's Quick Guide to Interpersonal Psychotherapy - by Myrna Weissman, Ph.D.
  

• Comprehensive Guide To Interpersonal Psychotherapy - by Myrna Weissman, Ph.D.
  

• Treatment for Chronic Depression: Cognitive Behavioral Analysis System of Psychotherapy (CBASP) - by James McCullough, Ph.D.
  

• Patient's Manual for CBASP - by James McCullough, Ph.D.
  

• Treating Chronic Depression with Disciplined Personal Involvement: Cognitive Behavioral Analysis System of Psychotherapy (CBASP) - by James McCullough, Ph.D.
  

• Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse - by Zindel Segal, Ph.D.

Mike Anestis is a doctoral candidate in the clinical psychology department at Florida State University

Antidepressant use has increased in the United States while psychotherapy use has decreased: Is this a healthy trend?

by Michael D. Anestis, M.S.

When I am contemplating my next article, I use a variety of resources to aid in my decision making process.  At times, I reflect on things I have read in the past that I think might be interesting.  Other times, I react to something I believe was misrepresented in popular media.  On other occasions, I browse newly released issues of prominent psychological journals and search for interesting findings.  Today, however, my article was prompted by a different resource.  While posting updates for PBB on Twitter yesterday, I noticed a user named BPDinOKC had posted a link to an article declaring that antidepressant use in the United States had spiked dramatically in recent years.  I followed up on this link and read a strong review of the study on the excellent website Psych Central.  I highly recommend following that link if you would like to read a more in depth summary of the findings.

The original source of this finding was a recent study by Mark Olfson and Steven Marcus, published in the current issue of Archives of General Psychiatry.  The authors reported that, between the years of 1996 and 2005, the use of antidepressant medications in the United States doubled from 13.3 million individuals to 27.0 million individuals.  Additionally, amongst individuals receiving antidepressant treatment, co-occurring prescriptions of antipsychotic medications increased whereas the use of psychotherapy declined.  It is not my goal today to go into further detail on these findings - the Psych Central article did a great job of accomplishing that task - but rather to provide some evidence that this trend is not our nation's best path towards decreasing the rates of depression onset and relapse.

Before presenting my evidence, let me preface this article with a bit of a disclaimer.  PBB wholeheartedly supports the use of pharmacological interventions when empirical evidence indicates that it is the best option.  In the case of depression, the focus of today's article, there is compelling evidence that antidepressant medications can be highly beneficial.  In this sense, we are not arguing against the use of medication in the treatment of depression, but rather attempting to clarify the entire picture so that individuals in need of help can more fully understand their options.

So...why did the finding that antidepressant use has doubled while psychotherapy use in that same population has declined prompt me to write an article?  Quite simply, because the evidence does not support the use of antidepressant medication in place of psychotherapy as a long term solution to depression. Below is a quick sampling of studies indicating that certain forms of psychotherapy are at least as effective as antidepressant medication in the treatment of depression:

• Keller and colleagues (2000) compared cognitive behavioral analysis system of psychotherapy (CBASP), nefrazadone (an antidepressant), and the combination of the two for the treatment of depression.  They found that, of those who completed the study, 85% of individuals who received both antidepressant medication and CBASP recovered from depression.  Only 55% of individuals receiving medication only and 52% of individuals receiving CBASP only recovered.

• DeRubeis and colleagues (2005) reported that, at 16 weeks, individuals receiving cognitive therapy (CT) had recovered from depression at the same rate (58%) as individuals receiving antidepressant medication.

• Dimidjian and colleagues (2006) found that behavioral activation was just as effective as antidepressant medication in the treatment of depression and both were superior to CT.

• Faramarzi and colleagues (2008) reported that cognitive behavioral therapy (CBT) was more effective than antidepressant mediation in treating depression in infertile women.

• Melvin and colleagues (2006) found that CBT was more effective than antidepressant medication in the treatment of depression, and that the combination of the two offered not significant benefits over CBT alone.

The above mentioned findings, on their own, are fairly compelling, but this is only the beginning of the story.  What these findings show is that, when an individual presents with depression, both antidepressant medication and various forms of CBT can effectively treat acute symptoms.  These findings, however, do not address the degree to which either approach to treatment prevents symptoms from coming back after treatment is over. 

Depression is, by nature, episodic.  In other words, it tends to flare up, recede, flare up again, and so on.  As such, simply being able to diminish symptoms is not enough.  Effective care must also prevent those same symptoms from reoccurring once treatment is over.  One way to do this would be to remain in treatment forever.  This is the approach taken by practitioners who prescribe antidepressant medications with no intention of ever discontinuing use for that patient.  Is this the best approach though?  The evidence says "no."  Below is another sampling of studies, this time with a focus on the degree to which various treatments prevent relapse:

• Bockting and colleagues (2005) found that including CT sessions after remission in clients treated with antidepressant medication significantly reduced rates of relapse at 2-year follow-up.  This was particularly true for individuals with a history of five or more prior depressive episodes, as relapse rates in this group decreased from 72% to 46%.
  

• Dobson and colleagues (2008) reported that, at 1-year follow-up, individuals who had received behavioral activation or CT or who were still taking antidepressant medication had relapsed at a significantly lower rate than individuals who had discontinued antidepressant use.  This same result was found at 2-year follow-up as well.

• Hollon and colleagues (2006) found that individuals withdrawn from CT were less likely to relapse (30.8%) than were individuals withdrawn from treatment with antidepressants (76.2%).  Additionally, individuals who had completed CT and were withdrawn from treatment following remission were no more likely to relapse than were individuals who continued to take antidepressant medications after remission.

This is only a small sampling of research on this point, but they are consistent with other results and these findings are the key in this entire debate.  Many individuals who argue for the use of antidepressant medication instead of CBT or its various alternative forms and components (e.g., CBASP, behavioral activation) maintain that symptom reduction occurs more quickly with antidepressants than in psychosocial approaches and, as such, is more cost effective.  The problem with this argument, however, is that an extremely high percentage of individuals treated with antidepressants relapse once they discontinue the use of their medication.  So, they either have to pay for medication permanently, which is in no way cost effective, or they can pay a smaller amount for acute treatment and face a substantial risk of relapse.  CBT, on the other hand, offers a short term (often 12-20, 1-hour weekly sessions) treatment that substantially reduces the risk or relapse without requiring ongoing treatment after remission.  That, in the long term, is significantly more cost-effective.

Again, it is important to point out here that I am not arguing against the use of antidepressants.  The evidence for their utility in treatment depression as well as other mental illnesses (e.g., obsessive-compulsive disorder) is strong.  The point, rather, is that antidepressants are no more effective than several psychotherapeutic approaches at reducing symptoms and are, in fact, worse than those approaches at preventing relapse.  As such, a trend towards increased antidepressant use and decreased psychotherapy use is not an overall positive development. 

It is great that more people are seeking treatment.  This indicates that the stigma of mental illness is decreasing and effective care is becoming more accessible.  At the same time, this trend indicates that many clinicians and individuals suffering from depression are unaware of all of their options for treatment and that many clinicians - particularly in primary care settings - are not providing consumers with their most effective paths towards sustained health.

If you would like to learn more about cognitive behavioral therapy, CBASP, or depression, we recommend the following resources, all of which are available through our online store:

Cognitive Therapy of Depression - Aaron Beck, M.D.

Feeling Good: The New Mood Therapy Revised and Updated - David Burns, M.D.

Treatment Plans and Interventions for Depression and Anxiety Disorders - Robert Leahy, Ph.D.

Cognitive Therapy Techniques: A Practitioner's Guide - Robert Leahy, Ph.D.

Treatment for Chronic Depression: Cognitive Behavioral Analysis System of Psychotherapy (CBASP) - James McCollough, Ph.D.

Patient's Manual for CBASP - James McCollough, Ph.D.

Handbook of Depression, Second Edition - Ian Gotlib, Ph.D. and Constance Hammen, Ph.D.

Mike Anestis is a doctoral candidate in the clinical psychology department at Florida State University.

SSRI treatment has no effect on the repetitive behaviors found in autism and autism spectrum disorders

by Joye C. Anestis   

Public interest and concern with autism and autism spectrum disorders (ASDs; e.g., Asperger's disorder) has taken off in the past several years.  It's always exciting when the media gets involved in a mental health topic and raises awareness about the conditions tackled by clinical psychologists.  Even though the media sometimes spreads misinformation about the condition du jour (e.g., recent publicity about a proposed link between vaccines and autism, a link that has been scientifically refuted), the publicity usually benefits the individuals and families struggling with mental disorders, as such attention results in understanding, acceptance, and, importantly, more funding for necessary research.  Autism and ASDs are the current condition du jour, with news sources and even entertainment outlets adding it into their storylines (for example, the past season of Grey's Anatomy included a doctor with Asperger's disorder).  As those of you reading this with a child or loved one with an autism spectrum disorder know, scientists are still struggling with appropriate treatments for autism and ASDs (a fact of life that I'm sure is overwhelmingly frustrating for caretakers).  One common component of treatment is antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs).  SSRIs are prescribed for autism and ASDs for a variety of reasons.  One primary reason is a supposed similarity between the repetitive behavior displayed in individuals with autism and ASDs and the compulsive behavior seen in obsessive-compulsive disorder (OCD; Hollander et al., 2005; Hollander, Phillips, & Yeh, 2003; McDougle et al., 1995), a disorder for which SSRIs are commonly prescribed.  Yet, very little is known about the utility of prescribing these medications to individuals with autism and ASDs.  Few studies have been conducted on their efficacy for these conditions, and most of the ones that have been conducted contain flaws which prohibit the drawing of firm conclusions.  To begin to fill in this research gap, Bryan King and colleagues conducted  the largest, most methodologically sound study of antidepressant use in children for autism and ASDs to date (the article can be found in the June 2009 issue of Archives of General Psychiatry).  King et al. (2009) examined the efficacy of citalopram hydrobromide, a commonly used SSRI (Celexa), in reducing repetitive behavior in children with ASDs.  Repetitive behavior was chosen as the outcome measure due the aforementioned theoretical link to OCD. 

149 children participated in the trial and were randomly assigned to receive citalopram (n = 73) or placebo (n = 76).  A liquid form of citalopram was administered based on a detailed dosing schedule, and the placebo matched for smell, taste, and viscosity.  Subjects had to be 5 to 17 years old and meet DSM-IV-TR criteria for autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specific (other PDDs were excluded, namely Rett's disorder and childhood disintegrative disorder).  These diagnoses were made with the most rigorous assessment instruments available, the Autism Diagnostic Interview Schedule - Revised and the Autism Diagnostic Observation Schedule.  Furthermore, subjects had to have at least a moderate illness severity rating on the Clinical Global Impressions scale and at least a moderate score on compulsive behaviors on the Children's Yale-Brown Obsessive Compulsive Scales modified for PDDs.  Detailed medication histories were obtained for each subject, and concurrent treatment with psychotropic medications or medications known to intersect with citalopram were not allowed (the only exception to this was some sleep medication).  Remarkably, most of the participants (82.6%) completed the 12-week trial. 

Contrary to their expectation, the authors found no significant differences between citalopram and the placebo at the end of 12 weeks on any of their outcome measures (there was one small change noted on one subscale of one of the 5 measures, but it was not a clinically significant change).  Thus, the medication was no better than placebo in changing repetitive behavior or overall severity of presentation.  Furthermore, the medication was associated with multiple side effects as compared to the placebo.  For those treated with citalopram, 97.3% reported at least 1 adverse side effect due to the treatment (see the article for a detailed list).  This finding is consistent with other studies showing elevated rates of side effects associated with psychotropic medications in this population.

Its unusual for a journal to report null findings (i.e., findings that do not support the hypotheses), but occasionally, studies are conducted in such a rigorous manner that null findings provide important information.  In the case of the present study, the lack of effect of citalopram on repetitive behaviors is a novel and important contribution.  As SSRIs are increasingly prescribed to help manage the symptoms of autism and ASDs, it necessary to know what effect it might have.  The current study suggests that at least citalopram is not an effective medication to deal with repetitive behavior and is likely to cause adverse effects.  The study also highlights the need for more rigorous investigations into medications before using them to treat or manage ASDs (and the same could be said for almost every other condition), as well as for alternative treatments for autism and ASDs. 

So what do we know about treatments for autism and ASDs?  Unfortunately, not a ton.  There are currently no empirically supported treatments for these conditions, but hopefully this will change in the near future.  If you are looking for treatment resources for your child or someone else, the National Institute of Mental Health offers tips (click here for the link).  I would love to hear your thoughts and comments on the current state of autism research or on the article discussed above. 

Joye Anestis is a doctoral candidate in clinical psychology at Florida State University.

A new study examines group CBT for ADHD in adults

by Joye C. Anestis

At PBB, we have written quite a bit about attention-deficit/hyperactivity disorder (ADHD) in an effort to spread knowledge that it is a legitimate diagnosis (albeit one that is often inappropriately diagnosed).  The clinical psychology field, in conjunction with psychiatry, is still trying to determine the best practices in treating this troublesome disorder.  In children, stimulant medication, behavioral parent training, and behavioral classroom interventions are all considered ESTs for ADHD.  Usually, these treatments are administered in combination to achieve the most comprehensive results.  For example, MTA (1999) found equivalent ADHD symptom reduction for a group treated with medication alone and a group treated with medication combined with behavioral treatments (behavioral parent training, behavioral classroom interventions, Pelham's summer treatment program).  Furthermore, children receiving the combined treatment experienced greater improvement in common non-ADHD domains, such as depression and anxiety, greater parental satisfaction with the treatment, and overall lower medication dosages. 

While large amounts of research is regularly conducted about ADHD in childhood, relatively little is known about the diagnosis and treatment of ADHD in adulthood.  Of the literature that does exist, most of it focuses on pharmacotherapy and little addresses the utility of psychotherapy, even though psychotherapy is known to be beneficial for children.  A recent study (Bramham et al. 2009) examined whether group CBT would be beneficial for adults with ADHD.  As is seen from the MTA study cited above, medication addresses the core ADHD symptoms, things like inattention, hyperactivity, and poor concentration.  Individuals with ADHD, however, also suffer from a variety of additional concerns that are not addressed by stimulant medications.  Adults with ADHD, for example, often suffer from comorbid depression, anxiety, and substance use; academic underachievement, problems with work, relationship difficulties, and problematic social interactions; and low self-esteem (importantly, these same problems also effect children with ADHD and might be exacerbated in adults who were not diagnosed in childhood).  Bramham et al. (2009) hypothesized that a group CBT program will help alleviate these accompanying problems.  Furthermore, the authors note that many adults do not fully respond to medication treatment, with 20-50% considered to be nonresponders and many only showing a 50% or less reduction in core ADHD symptoms. 

The sample: 61 (40 males, 21 female; mean age = 32.95) Caucasian individuals diagnosed with ADHD in adulthood were assigned to receive group CBT + medication (although 2 of this group opted for CBT without medication).  The investigators did not administer the medication as part of the study.  Participants just continued the medication they were already taking.  Most of the group had never received psychotherapy before.  One-third (n = 20) of the participants dropped out during treatment.  A second group of participants were placed on a wait-list for the treatment and so received medication only.  This group consisted of 37 Caucasian clients (21 males, 16 females; mean age = 31.19).  Oddly, the authors did not mention why the sample was not racially/ethnically diverse.

The treatment: The CBT group treatment attended 6 consecutive ADHD workshops.  Session 1 focused on psychoeducation about "what it means to have ADHD."  Session 2 focused on anger and frustration, with an overall goal of targeting the low frustration tolerance that can lead to explosive outbursts in individuals with ADHD.  Session 3 centered on emotions, primarily focusing on the connections between mood, thoughts, and behaviors and teaching skills to improve mood by examining this cycle.  Session 4 was concerned with social and relationship skills.  As a group, the participants discussed ways in which ADHD symptoms have hampered their interpersonal performance. The group format also provided an opportunity to practice social skills in a safe environment.  Session 5 centered on practical approaches to time management and problem solving.  The last session again offered psychoeducation, this time addressing the future with ADHD.

The results: The group who received CBT + medication had significantly greater self-report ratings of self-efficacy and self-esteem and significant improvement in knowledge about ADHD.  The individuals who received CBT also rated the workshops as beneficial, and especially noted that getting to know others with the disorder was helpful.  Both groups showed improvement in anxiety and depression symptoms.

This is certainly an imperfect study, with quite a few serious methodological concerns (e.g., no random assignment, no psychotherapy control group).  Still, as we have yet to determine an EST for adult ADHD, these findings mark an important step toward determining how to help.  Especially in this age of managed care, identifying useful group interventions is certainly prudent.  Group interventions are generally shorter and cheaper, making them attractive to managed care companies and clients, while allowing psychologists to treat a greater number of clients.  For more information on treatments for ADHD, checkout our online bookstore!

Joye Anestis is a doctoral candidate in clinical psychology at Florida State University.