Issue 63, Jul 2017
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Psychodynamic therapy is not less effective than other treatments

Steinert C, Munder T, Rabung S, Hoyer J, Leichsenring F. Psychodynamic Therapy: As Efficacious as Other Empirically Supported Treatments? A Meta-Analysis Testing Equivalence of Outcomes. Am J Psychiatry. 2017 May 25:appiajp201717010057. [Epub ahead of print] PubMed PMID: 28541091.

Background

Psychodynamic psychotherapy has been shown in randomized controlled clinical trials to work when compared to “placebo” interventions.

But how does it compare to other treatments like cognitive-behavior therapy? Previous meta-analyses have been contradictory about whether or not psychodynamic therapy works as well as cognitive-behavior therapy does.

This meta-analysis systematically evaluated whether psychodynamic psychotherapy works as well as other treatments-- cognitive-behavioral therapy or medications.

Methods

This meta-analysis had many strengths in terms of its methodology. Here are two of them:

1. Clinical trials use research design and statistical analysis methods to evaluate whether or not one treatment is more efficacious than another. However, when no statistically significant difference is found between two interventions, this does not necessarily mean that the two treatments are equivalent. It just means that the study was not able to show a difference. This is because to evaluate whether or not two treatments are equivalent requires specific approaches in the research. This is the first study to systematically evaluate one form of psychotherapy versus other established treatments by formally applying the research methods of equivalence testing.

2. The term “researcher allegiance” refers to the problem that those whose expertise focuses on researching a particular treatment (e.g., cognitive-behavior therapy or psychodynamic therapy) are more likely to publish analyses suggesting that their particular treatment works better than other treatments. This study controlled for researcher allegiance because it was a collaboration between researchers with expertise in cognitive-behavior therapy and those with expertise in psychodynamic psychotherapy. The authors refer to this using the interesting term “adversarial collaboration.”

Since this study was aimed at testing equivalence of the treatments being compared, the authors defined in advance how much of a difference between two treatments they would consider to be a “real” or meaningful difference.

A systematic search of the literature was conducted for relevant studies.

Independent raters assessed the clinical trials found.

The studies were statistically combined using meta-analysis.

Results

Twenty-three randomized controlled trials, in which 2,751 patients had participated, were included in this meta-analysis.

A wide variety of disorders had been treated in these clinical trials: depressive disorders, anxiety disorders, eating disorders, substance use disorders, and personality disorders.

The main finding of this study was that psychodynamic psychotherapy was shown to be equivalent to the comparison treatments (mainly cognitive-behavior therapy). That is, neither treatment was superior to the other.

In statistical terms, this was demonstrated by finding that the 90% confidence intervals, a more conservative measure, were less than the pre-specified thresholds for what would constitute a difference, i.e., a Hedge’s g of 0.25. In other words, neither treatment was superior to the other with a difference corresponding to a Hedge’s g of 0.25 or greater.

The results were similar across the various disorders studied.

Conclusions

Using rigorous methodology, this meta-analysis showed that psychodynamic psychotherapy was as efficacious as cognitive-behavior therapy or medications.

The findings were more robust for cognitive-behavior therapy than for medications since only two studies had compared psychodynamic therapy to a medication.

Clinical Commentary

This paper should give solace to those who practice and/or research short-term or time-limited psychodynamic therapy.

While most of the studies included in this analysis provided equal number of sessions for cognitive-behavior and psychodynamic therapies, in some of them, the number of sessions was greater for those receiving psychodynamic therapy. Even in shorter term treatment models, psychodynamic therapy may require more sessions than cognitive-behavior therapy.

In the US, billing codes and reimbursement for the different types of psychotherapy are the same. However, health insurances may limit the total number of sessions of psychotherapy that they pay for per year. Therefore, access to longer-term psychodynamic psychotherapy continues to be a problem for many patients.

In this analysis, only clinical trials that used manual-guided psychotherapy were included. Of course, in clinical practice, manual-guided psychotherapy is not commonly used, especially not for psychodynamic therapy. In my opinion, adoption of manual-guided psychotherapy can be a major advance in the quality of psychotherapy training and practice.

The clinicians providing psychotherapy, both psychodynamic and cognitive-behavior therapy, in clinical trials may have different levels of expertise than clinicians in general. Therefore, all psychotherapy studies have more difficulty generalizing to routine clinical practice than studies in psychopharmacology.

While overall the treatments were equally efficacious, it is possible (and probably likely) that one type of treatment may be more efficacious than another for some patients with some conditions. This is what future research should focus on.

In the meanwhile, when one treatment modality is not helpful, it is probably clinically wise to consider a different modality.

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Can C-reactive protein levels tell us which antidepressant to prescribe?

Jha MK, Minhajuddin A, Gadad BS, Greer T, Grannemann B, Soyombo A, Mayes TL, Rush AJ, Trivedi MH. Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. Psychoneuroendocrinology. 2017 Apr;78:105-113. PubMed PMID: 28187400.

Background

It has been frustrating to clinicians, patients, and their families that it is hard to predict in advance which treatment may work better for which patient.

Since inflammation is now known to play a role in some patients with major depressive disorder, this study aimed to assess whether levels of inflammatory markers like C-reactive protein were associated with a preferentially better response to treatment with either an SSRI or a combination of an SSRI and bupropion.

Methods

This study was a secondary analysis of data from a randomized, controlled clinical trial called the Combining Medications to Enhance Depression Outcomes (CO-MED) trial.

Various inflammatory markers were measured prior to treatment only in a subset of these patients with major depressive disorder who agreed to participate in the add-on study. That is why this paper is based on data on 106 patients rather than all patients who participated in the CO-MED study.

After baseline assessment, these participants were randomly assigned to receive either:

1. Escitalopram plus placebo (n=51) or

2. Escitalopram plus bupropion (n=55)

Results

At baseline (before treatment), 70% of the patients had increased levels of C-reactive protein (> 1 mg/L), which indicate systemic inflammatory activity.

Overall, participants in both treatment groups improved equally and had similar side effect burden.

The main finding of this paper is that higher levels of C-reactive protein at baseline were correlated with lower depression severity (correlation coefficient = -0.63) after treatment with the combination of escitalopram and bupropion.

On the other hand, participants with C-reactive protein levels less than 1 mg/L had greater improvement with escitalopram monotherapy than those with C-reactive protein levels of 1 mg/L or more.

Overall, the depression remitted in 42% of the participants in this study. But, as the table below shows, the remission rates for depression in different subgroups were quite different:

  C-reactive protein level at baseline
  < 1 mg/L 1 mg/L or more
   Escitalopram 57% 30%
   Escitalopram + Bupropion 33% 51%

  

These are big differences.

The investigators then calculated what the outcomes would have been if, hypothetically, the patients had been assigned to the treatments based on the C-reactive protein level at baseline. That is, if they had received escitalopram alone if the C-reactive protein was < 1 mg/L and the escitalopram-bupropion combination if the C-reactive protein was 1 mg/L or more.

It was estimated that if this had been done, the overall remission rate would have been 53% (compared to the observed remission rate of 42% of participants).

The other inflammatory markers studied were not associated with the outcomes of treatment.

The side effect burden was also not related to any inflammatory marker measured at baseline.

Conclusions

C-reactive protein levels measured before treatment may indicate better outcomes with the combination of escitalopram and bupropion rather than with escitalopram alone.

Clinical Commentary

Before being accepted, this finding needs to be confirmed in prospective double-blind studies in which participants receive treatment based on baseline C-reactive protein levels.

Also, this study measured C-reactive protein in only 106 patients, so confirmation in larger studies is needed.

If the findings are confirmed, they could be a valuable addition to clinical practice given that measurement of C-reactive protein requires a simple blood test and that we have very few other markers of preferential response to a particular treatment.

As I have noted on several occasions in previous editions of “GME Research Review,” a simple rule of thumb is that an intervention that leads to a 10% or greater difference in an outcome is generally considered clinically useful. Of course, this judgment also depends on how simple or harmless the intervention is and on how important the outcome is.

From that viewpoint, if choosing to use a combination of an SSRI and bupropion for patients with major depressive disorder whose C-reactive protein is elevated at baseline can lead to an 11% improvement in remission rates (the estimated 53% versus the actual 42%), we would consider this a clinically useful way of deciding which treatment approach to use.

It should be noted that 70% of the patients in this study had C-reactive protein levels of 1 mg/L or greater at baseline. Based on the findings of this study, doesn’t that seem to imply that for the majority of patients with major depressive disorder a combination of an SSRI and bupropion may be better than an SSRI alone? This is an interesting point for us to think about.

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Atomoxetine may be particularly useful for inattention in adults with ADHD

Ravishankar V, Chowdappa SV, Benegal V, Muralidharan K. The efficacy of atomoxetine in treating adult attention deficit hyperactivity disorder (ADHD): A meta-analysis of controlled trials. Asian J Psychiatr. 2016 Dec;24:53-58. PubMed PMID: 27931908.

Background

Atomoxetine is approved by the FDA for the treatment of ADHD in both children and in adults.

Adults with ADHD present with symptoms that are different in some ways from those that children with ADHD have.

This meta-analysis aimed to evaluate the efficacy of atomoxetine for ADHD in adults. In particular, it aimed to evaluate the efficacy of atomoxetine for different symptoms domains in adults.

Methods

A literature search was done though this based only on searching MEDLINE.

Randomized, controlled clinical trials comparing atomoxetine to placebo for the treatment of ADHD in adult patients were identified.

A meta-analysis was done to statistically combine the results of these studies.

Results

Thirteen randomized controlled clinical trials, in which 1824 patients had participated, were included in this meta-analysis.

Not surprisingly given that it is FDA-approved for the treatment of ADHD, atomoxetine was more efficacious than placebo for improvement in overall ADHD scores. The standardized mean difference, a measure of effect size, was – 0.45, indicating a small-to-moderate effect.

What about the efficacy of atomoxetine for specific symptom domains of ADHD? Atomoxetine was efficacious for both inattention (effect size 0.42) and impulsivity/hyperactivity (effect size 0.36).

But atomoxetine was statistically significantly more efficacious for treating inattention than for treating hyperactivity/impulsivity.

Conclusions

Atomoxetine is efficacious for treating ADHD in adults, but more so for treating inattention than for treating hyperactivity/impulsivity.

Clinical Commentary

The finding that atomoxetine is particularly efficacious for inattention is important because in adults with ADHD, impulsivity and inattention are more of a problem than hyperactivity is. Also, while other symptoms tend to improve with age, inattention not only persists but also may, in fact, increase with age.

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Can we predict who will develop postpartum depression?

Suri R, Stowe ZN, Cohen LS, Newport DJ, Burt VK, Aquino-Elias AR, Knight BT, Mintz J, Altshuler LL. Prospective Longitudinal Study of Predictors of Postpartum-Onset Depression in Women With a History of Major Depressive Disorder. J Clin Psychiatry. 2017 Mar 14. [Epub ahead of print] PubMed PMID: 28297589.

Background

Women with a history of major depressive disorder are at higher risk of postpartum major depression. About a third of women with a history of major depression prior to pregnancy suffer from major depression during the postpartum period, which is about two to three times the risk in other postpartum women.

This study aimed to assess factors during the third trimester that may be associated with increased risk of major depression during the postpartum period.

For example, if women with a past history of major depression don’t meet criteria for major depression during the third trimester, are they still at higher risk of major depression during the postpartum period?

Also, if women with a past history of major depression are taking an antidepressant medication during the third trimester, are they at lower risk of major depression during the postpartum period?

Methods

Participants were 300 women with a past history of major depressive disorder prior to the pregnancy who were prospectively evaluated during the third trimester and after delivery.

The study evaluated variables during the third trimester that may predict the presence of major depression during the postpartum period.

Results

Among these participants, though they had suffered from major depression prior to the pregnancy, only 15% of them met criteria for major depressive disorder during the third trimester.

In the 85% of women who did not meet full criteria for major depression in the third trimester, the severity of depression symptoms (based on the Hamilton Depression Rating Scale total score) nevertheless predicted the presence of major depression during the postpartum period.

In particular, presence during the third trimester of three types of symptoms (three items on the Hamilton Depression Rating Scale) was associated with presence of major depression during the postpartum period:

1. Early insomnia

2. Decreased interest or engagement in work or other activities

3. Suicidal ideation

Patients who were taking an antidepressant medication during the third trimester (at the discretion of the patient and her clinician), were not found to be at lower risk of having major depression during the postpartum period.

Conclusions

This is the largest prospective study to date that evaluated the risk of postpartum depression in women who had a prior history of major depression but did not meet criteria for major depression during the third trimester.

Among women with a history of major depressive disorder who do not meet criteria for major depressive disorder during the third trimester, this study suggests that taking an antidepressant may not reduce the risk of major depression during the postpartum period.

Clinical Commentary

This study suggests that women with a prior history of major depressive disorder should be evaluated for depressive symptoms during the pregnancy even if they don’t meet full criteria for major depressive disorder. Appropriate monitoring and follow up should be set up.

However, I don’t think we can definitely conclude from this study that taking an antidepressant during the third trimester has no protective effect against major depression in the postpartum period. This is because, as noted above, in this study patients were not randomized to receive or not receive an antidepressant. The decision to take an antidepressant or not was made by the patients and their prescribing clinicians independently of the study.

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Should we discourage marijuana use in patients with depression?

Bahorik AL, Leibowitz A, Sterling SA, Travis A, Weisner C, Satre DD. Patterns of marijuana use among psychiatry patients with depression and its impact on recovery. J Affect Disord. 2017 Apr 15;213:168-171. PubMed PMID: 28242498; PubMed Central PMCID: PMC5407687.

Background

It is known that persons with depressive disorders commonly use marijuana. Depression is associated with a six-fold higher risk of marijuana-related problems.

But, in contrast to alcohol, whether marijuana use affects recovery from the depression has not been adequately studied.

This study evaluated the effect of marijuana use on the outcome of depressive symptoms (not major depression) in persons being treated for substance use disorders

Methods

Over 300 outpatients with “depression” participated in this study. For the purposes of this study, depression was defined as a score of 5 or more on the PHQ-9 questionnaire.

Note: this criterion was lower than a score of 10 or 12 on the PHQ-9 that is commonly considered to correlate with a diagnosis of major depression.

These patients were participating in a randomized controlled trial of motivational interviewing for alcohol/drug use treatment in depressed patients.

At each visit (baseline, 3 months, and 6 months), the following were assessed:

1. Severity of depression and anxiety

2. Functional impairment

3. Marijuana use in the 30 days prior to the visit

Results

Of these patients, 41% had used marijuana in the previous 30 days.

Over the next six months, overall, the use of marijuana decreased. However, in those who were more depressed and in those who were older than 50 years of age, marijuana use was more likely to increase over the six months of follow up.

Those who used marijuana had worse outcomes in terms of both depression and anxiety. They also had worse functioning related to their mental health.

Not surprisingly, use of medical marijuana (27% of the sample) was associated with worse functioning related to physical health.

Conclusions

Marijuana use is common among mental health outpatients substance use disorders who also have depressive symptoms. This is particularly true for younger patients.

Marijuana use in these patients was associated with poorer outcomes in terms of symptoms of depression and anxiety.

Clinical Commentary

I have been asked many times by my patients as to whether it was important for them to stop smoking marijuana. We need better, scientifically valid answers, rather than knee-jerk responses.

With regard to the findings of this study, we must remember that association does not mean causation. That is, we cannot be sure from this study that it was the marijuana use per se that led to the worse outcomes for symptoms of depression and anxiety.

Nevertheless, the results do suggest that marijuana use may not be benign in persons with depressive symptoms. We should assess all patients with depressive symptoms for their marijuana use and discuss with them the possibility that the marijuana use may be contributing to continued symptoms of depression and anxiety. Such discussions are likely to become more and more important as marijuana is legalized in more states because use of marijuana may become widely seen as “normal”.

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Rajnish Mago, MD
Medical Editor, GME Research Review

GME Research Review is a monthly newsletter edited by Rajnish Mago, MD, who is author of "The Latest Antidepressants" and "Side Effects of Psychiatric Medications: Prevention, Assessment, and Management." Dr. Mago selects, summarizes, and provides a clinical commentary on the latest published research in psychiatry. 

We are always carefully evaluating which research papers to discuss in GME Research Review. Have come across a research paper published in the last 6 months that you thought is clinically relevant? Do you want me to analyze it for you and for the benefit of others? Please email Dr. Mago the citation at [email protected].

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