GME Research Review – January 2016

GME Research Review is a monthly newsletter edited by Rajnish Mago, MD, who is Associate Professor of Psychiatry at Thomas Jefferson University and 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 you come across a research paper published in the last 6 months that you think is clinically relevant? Do you want me to analyze it for you and for the benefit of others? Please email me the citation at rajnishmago@gmail.com


Which disorders does psychodynamic psychotherapy work for?

Leichsenring et al. The empirical status of psychodynamic psychotherapy – an update: Bambi’s alive and kicking. Psychother Psychosom. 2015;84(3):129-48. PubMed PMID: 25833321.

Why is this study important?

  • While practice guidelines emphasize cognitive-behavior therapy, psychodynamic therapy is often emphasized in psychiatry residency programs and is widely practiced, at least as part of an eclectic approach.
  • In discussions of “evidence-based psychotherapies,” psychodynamic psychotherapy is often excluded.
  • It is important, therefore, for both trainees and practitioners to have some understanding of the research support for psychodynamic therapy – where it exists and where it does not.

Background

  • What qualifies as an evidence-based psychotherapy? Rigorous criteria for this have been proposed and improved upon. A key tenet of these criteria is that two randomized controlled trials showing efficacy are required for a treatment to be called “efficacious” and one randomized, controlled trial for it to be called “possibly efficacious”.
  • This paper applies these criteria to present an update on the evidence for psychodynamic therapy in specific mental disorders.

Methods

  • A systematic search of the literature was performed to identify relevant articles.
  • Criteria for including articles were ones where:
    1. A randomized, controlled trial evaluated psychodynamic therapy as a treatment for a specific problem in adults.
    2. Reliable and valid measures for diagnosis and outcome were used.
    3. Treatment manuals or manual-like guidelines were used to deliver the psychotherapy.
    4. Psychodynamic therapy was found to be either superior to no treatment/placebo/alternative treatment OR found to be equivalent to an established treatment.

Results

  • A total of 39 randomized, controlled trials met the inclusion criteria.
  • Psychodynamic therapy has been shown to be efficacious in:
    1. Major depressive disorder
    2. Social anxiety disorder
    3. Borderline personality disorder
    4. “Heterogeneous” personality disorders
    5. Somatoform pain disorder
    6. Anorexia nervosa
  • For major depressive disorder, psychodynamic therapy has also been shown to be efficacious in combination with pharmacotherapy.
  • For some disorders, only one RCT was found and, therefore, psychodynamic psychotherapy should be considered possibly efficacious but not definitely shown to be efficacious. These disorders were:
    1. Dysthymia
    2. Complicated grief
    3. Panic disorder
    4. Generalized anxiety disorder
    5. Substance abuse/dependence.
  • Lastly, for some disorders, psychodynamic psychotherapy has not been shown in RCTs to be efficacious:
    1. Obsessive-compulsive disorder
    2. Posttraumatic stress disorder
    3. Bipolar disorder
    4. Schizophrenia spectrum disorders.
  • No direct comparisons of psychodynamic therapy alone with pharmacotherapy alone are available.

Conclusions

  • Evidence has emerged that psychodynamic therapy is efficacious or possibly efficacious in a wide range of common mental disorders.
  • Further research is required for those disorders for which sufficient evidence does not yet exist.

Clinical Commentary

  • The authors note that there is a lot of overlap between interventions even when the psychotherapy is delivered in a manualized, i.e., standardized fashion. For example, cognitive-behavioral therapists use interpretations or clarifications as often as psychodynamic therapists. Similarly, psychodynamic therapists have been found to adhere to a CBT prototype to the same extend as they adhered to a psychodynamic prototype.
  • BUT, what is most important is not whether similar things are done in different types of psychotherapy but which of the interventions are associated with the benefit of the psychotherapy. In many studies, the psychodynamic interventions have been shown to be associated with the good outcome. Also, it has been found that changes in psychodynamically relevant mediators such as core conflicts or insight are significantly related to good outcomes.

Why do we eat more sugar when under stress?

Tryon et al. Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body. J Clin Endocrinol Metab. 2015 Jun;100(6):2239-47. PubMed PMID: 25879513.

Why is this study important?

  • Obesity is a huge problem in society in general and in particular in persons with mental health problems.
  • Excessive consumption of sugar plays a key role in weight gain.
  • Also, many of our patients – especially those with atypical depression – report sugar cravings.
  • Thus, sugar cravings are of great interest to the mental health clinician.

Background

  • Consuming sugar in response to being stressed is a habit that is difficult to break. But why?
  • Rodent studies suggest that sugar consumption may activate a negative feedback pathway that may turn off the stress response and thereby reinforce habitual sugar overconsumption.
  • Aim: To evaluate how consuming sugar affects response to stress.

Methods

  • This was a randomized, double-blind controlled clinical trial.
  • The study was conducted in a University setting.
  • Nineteen women (18- to 40-years-old) with a body mass index of 20 to 34 Kg/m2 were enrolled. (Note: normal BMI is 18.5 to 25 Kg/ m2)
  • For 2 weeks, these women consumed a beverage three times a day that contained either sucrose or aspartame. They were told not to consume any other sweetened beverages including fruit juices.
  • A stressful task – the Montreal Imaging Stress Task – was given. Briefly, this involves doing timed mental arithmetic and the subject being socially evaluated.
  • Changes in salivary cortisol and in brain responses (on functional MRI) in response to the stressful task, were measured.
  • In addition, a naltrexone challenge was used. Increased nausea and rise in cortisol after taking naltrexone indicates weak opioid tone.

Results

  • Sucrose consumption was associated with higher stress-induced increase in activity in the left hippocampus. Note: normally, stress reduces activity in the hippocampus.
  • Sucrose consumption for 2 weeks was associated with reduction in the stress-induced increase in cortisol.
  • The sucrose group also had a lower reactivity to naltrexone in the form of lower nausea, suggesting higher opioid activity in the brain.

Conclusions

  • This is the first study to show that consumption of sugar but not artificial sweetener inhibits stress-induced cortisol secretion.
  • Also, consumption of sugar inhibited the usual stress-induced decrease in activity in the hippocampus and increased opioid tone in the brain.
  • It seems that there is a negative feedback pathway that is affected by sugar.
  • This may make explain why many persons are more likely to use sugar-containing foods and beverages when under stress.

Clinical Commentary

  • Knowing the strong biological basis for the reinforcing effects of sugar consumed under stress can make us more empathetic towards our patients (and ourselves!).
  • Attempts to reduce excessive sugar consumption and obesity must include stress reduction and stress management strategies.

Does psychotherapy for major depression work as well as claimed?

Driessen et al. Does Publication Bias Inflate the Apparent Efficacy of Psychological Treatment for Major Depressive Disorder? A Systematic Review and Meta-Analysis of US National Institutes of Health-Funded Trials. PLoS One. 2015 Sep 30;10(9):e0137864. PubMed PMID: 26422604

Why is this study important?

  • It is obviously important to get an accurate estimate of the efficacy of different treatments so that the best treatments can be recommended.
  • There was a big scandal in the recent past when data was published showing that the efficacy of antidepressant medications had been exaggerated, in part due to negative studies not getting published (e.g., Turner et al., 2008).
  • Now, a study found that the same thing has happened for psychotherapy. This has led to a lot of attention for this study in the press. Your patients may ask you about it too!

Background

  • This is the first study to directly compare the effects of psychotherapy for major depression in published studies versus after including unpublished studies.

Methods

  • The authors identified grants from the United States National Institutes of Health to fund randomized clinical trials comparing a psychological treatment to control conditions or to other treatments in patients diagnosed with major depressive disorder.
  • The period covered was 1972 to 2008.
  • They then found out whether or not those grants led to publications.
  • For studies that were not published, they requested the data from the investigators of those unpublished studies.
  • Then, they did their own meta-analysis of the data including both published and unpublished studies.

Results

  • Of 55 research grants awarded that did start the clinical trial, 23.6% did not result in publications.
  • When the unpublished studies were added to the analysis, the efficacy of psychological treatments for major depression was reduced by 25% from what it was thought to be before the unpublished studies were added to the analysis.
  • The effect size for efficacy of psychotherapy for major depression based on published studies only was 0.52. When the unpublished findings were added to the published findings, the effect size was reduced to 0.39. 0.39 is 75% of 0.52. That’s why the authors say that the efficacy decreased by 25% when unpublished studies were included.

Conclusions

  • By ignoring the unpublished studies, previous meta-analyses have in the past overestimated the efficacy of psychotherapy for major depression by 25%.

Clinical Commentary

  • The efficacy of psychological interventions for major depression has been overestimated in the published literature. This is the same problem and for the same reasons that has been shown for antidepressant medications. For example, Turner et al. (2008) had found that omission of unpublished studies had led to overestimation of the efficacy of antidepressant medications by 24%, almost exactly the same as was found for psychotherapy in this study.
  • This study was not done by proponents of antidepressant medications “getting back” for the previous report showing publication bias with regard to antidepressant medications. No conspiracy theories, please! The authors are themselves psychologists who conduct research on psychotherapy.
  • It is very important to note that the findings of this study do not mean that psychotherapy does not work for major depression. They only mean that it did not work as well as we thought it had. The degree of the difference was not such that it would greatly affect our decision to use or not use psychotherapy for major depression.
  • It should also be noted that this meta-analysis only refers to treatment of major depression. It does not have any bearing on treatment of other forms of depressive disorders (e.g., dysthymia) with psychotherapy.
  • Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the both antidepressants and psychotherapy for major depression.
  • The authors noted that in this study they could not assess whether there was also another kind of bias. Could it be that not only were the studies that did not find psychotherapy to be as efficacious remain unpublished, but that even in the published studies, those outcome measurements that did not find psychotherapy to be as efficacious may have been left out of the papers?
  • For that, the authors suggested that funding agencies and journals should archive both the original study protocols and raw data from treatment trials. By comparing these to the published data, any bias in reporting outcomes could be detected and corrected.

Should we insist that our patients get ultrabrief pulse ECT?

Tor et al. A systematic review and meta-analysis of brief versus ultrabrief right unilateral electroconvulsive therapy for depression. J Clin Psychiatry. 2015 Jul 21. [Epub ahead of print] PubMed PMID: 26213985.

Why is this study important?

  • Electroconvulsive therapy (ECT) remains an important treatment modality that we should refer our patients for when clinically appropriate.
  • However, one of the important reasons why many patients are reluctant to get ECT is cognitive impairment.
  • If there is a type of ECT treatment that has lesser risk of cognitive adverse effects, this would make the treatment more palatable to patients.
  • Right unilateral (RUL) electrode placement has less cognitive adverse effects than bilateral ECT. Also, brief pulse square waveform stimuli lead to less cognitive adverse effects than sine wave stimuli. Moving from sine wave to brief pulse waveform was an important advance in ECT.
  • More recently, ultra brief pulse (UBP) stimulation has been developed where each pulse is only about 0.3 seconds versus 0.5 to 1.3 milliseconds for brief pulse stimuli.

Background

  • Ultrabrief pulse (UBP) right unilateral (RUL) ECT is being increasingly used for the treatment of depressive disorder.
  • Is it true that UBP-RUL ECT has lesser cognitive side effects?
  • Is it as efficacious as standard brief pulse (BP) RUL ECT?
  • Since several smaller studies have been done and the results have been conflicting, this paper did a systematic review and meta-analysis of the studies to answer these questions.

Methods

  • Multiple databases were systematically searched for relevant studies comparing UBP-RUL ECT to BP-RUL ECT for depressive disorders.
  • Papers included were those in English, which can be source of bias since clinical trials published in other languages (e.g., Japanese) are just as relevant as those published in English
  • The papers included were published by June 2013. Knowing this lets us know that we must check to see if any study has been published since then.
  • Six studies met the inclusion criteria; 689 patients were evaluated in these clinical trials.

Results

  • The mean number of ECT sessions given was greater for UBP-RUL ECT (9.6 sessions) than for BP-ECT (8.7)
  • BP-RUL ECT was slightly more efficacious in treating depression than UBP-RUL ECT. The effect size was 0.25 (small), for those who understand that concept. But, clinicians can understand how much of a difference there was by looking at the differences in response and remission rates (below).
  • When only the four studies that were randomized and double blind (i.e., higher quality) were included, there was no statistically significant difference in efficacy.
  • At the end of ECT treatment, response rates (50% or greater reduction in severity of depression) were 58% for BP-RUL ECT and 55% for UBP-RUL ECT.
  • Rates of remission (minimal remaining symptoms of depression) were 45% for BP-RUL ECT and 34% for UBP-RUL ECT.
  • However, UBP-RUL ECT resulted in less cognitive adverse effects. The largest advantages were for anterograde learning and recall, but there was an advantage in other cognitive domains that were evaluated as well, i.e., global cognition, retrograde memory.
  • The effect size was the advantage of lesser cognitive adverse effects was moderate for most measures (0.36 to 0.56).

Conclusions

  • BP-RUL ECT was slightly more efficacious than UBP-RUL-ECT in treating depression and required fewer treatment sessions, but led to greater cognitive side effects.

Clinical Commentary

  • As referring clinicians, we should be aware of these differences between BP-RUL ECT and UBP-RUL ECT.
  • Important! Not all institutions have UBP ECT and will probably not tell you or your patient that this is even an option.
  • If I put myself in the patient’s shoes, unless it was an emergency situation, I think I would insist on going to a place where UBP-ECT was available. So, I am going to insist on that for my patients as well.

Did you find these research summaries clear and easy to understand? Did you find them clinically useful? Your feedback is very important! Please send me your thoughts at rajnishmago@gmail.com.

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