Research Updates in Psychiatry

Research Updates in Psychiatry


IPT for Patients with Early Trauma Histories?

We know that psychotherapy is generally effective for depression, but we don’t really know which depressed patients will respond better than others. In a recent study, 124 depressed inpatients were randomly assigned to antidepressant medication, plus either a) interpersonal therapy (IPT) for five weeks (15 individual sessions and 8 group sessions), or b) basic clinical management (CM) sessions for 20 to 25 minutes three times per week.

Unsurprisingly, after five weeks, IPT + med patients improved significantly more than CM + med patients both in terms of improved score on the Hamilton Rating Scale for Depression (HAM-D) and in terms of HAM-D response rates: 70% for IPT vs 51% for CM. The IPT advantage held up when patients were reassessed one year later, though at five year follow up there was no longer any difference in HAM-D scores.

As part of their a priori statistical plan, the authors also had patients complete a measure of childhood trauma. Interestingly, IPT outperformed CM among patients who reported moderate to severe early trauma, but the two treatments had similar results among patients who did not report such trauma (Zobel I et al, Acta Psychiatr Scand online ahead of print).

TCPR’s Take: IPT may have reasonably strong long-term efficacy for depression—though this particular form of IPT was very intensive, and it’s unclear if the results generalize to depressed outpatients. IPT’s superiority in patients with early trauma histories aligns with a study which found that cognitive-behavioral analysis (a form of CBT) was more effective than nefazodone (Serzone) among patients with early trauma (Nemeroff CB et al, Proc Natl Acad Sci 2003;100(24):14293–14296). Patient reports of trauma history are not always accurate, but they may tell us which patients are particularly good candidates for psychotherapy.


Antipsychotics May Shrink Brains of Schizophrenics

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A recently published book by Robert Whitaker, Anatomy of an Epidemic, argues that modern psychiatric medications have been correlated with increasing, rather than decreasing rates of psychiatric disability, and that they might cause more harm than good. The book, carefully researched and written by a respected journalist, has generated heated debate (see, for example, The Carlat Psychiatry Blog review at http:// Now, as if timed to draw more interest to Whitaker’s controversial hypothesis, a study has been published that appears to show that antipsychotic treatment actually shrinks the brain.

As part of the Iowa Longitudinal Study, 211 patients with schizophrenia were enrolled in a naturalistic study in which their brains were scanned with an MRI several times over an average of seven years. Meanwhile, these patients were interviewed every six months in order to find out what medications they were taking, what dosages, how they were doing, etc. This huge database allowed researchers to determine what happens in the brains of schizophrenics over time, and, most crucially, to determine whether the changes might be related to the underlying disease process vs the action of antipsychotic medications.

The results were disquieting. Antipsychotic treatment was associated with decreased total brain volume, as measured by decreased total cerebral white matter, decreased frontal gray matter, and increased volume of the lateral ventricles. These results held even when possible confounding factors were controlled for—such as illness severity, illness duration, and substance abuse. Furthermore, greater exposure to antipsychotics—whether typical or atypical—was correlated with greater brain tissue reduction (Ho B, Arch Gen Psychiatry 2011;68(2):128-137).

TCPR’s Take: The authors acknowledge that this correlation of antipsychotic treatment with brain shrinkage does not prove causality. A randomized controlled study, in which patients are assigned medication vs placebo, and then followed with MRIs for years, would be needed for this. Such a study has not been done. Nonetheless, the authors point out that their results do agree with such controlled studies done in monkeys, in which haloperidol (Haldol) and olanzapine (Zyprexa) have caused 8% to 11% decreases in brain weight as compared to sham treatment.

In an accompanying editorial, Dr. David Lewis proposes the intriguing notion that maybe brain loss is actually good for schizophrenia and is part of the cure. He cites research showing that during normal adolescence, there is some loss of gray matter accompanying greater cognitive capacity.

Nonetheless, the take home point is that long term antipsychotic treatment may shrink brains—a possibility that should make most of us strongly consider other alternatives for off-label uses such as non-refractory depression, anxiety, and insomnia, and reserve antipsychotics for patients who are actually psychotic or manic.

Research Updates in Psychiatry

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This article was published in print 5/2011 in Volume:Issue 9:5.

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APA Reference
Psychiatry Report, T. (2013). Research Updates in Psychiatry. Psych Central. Retrieved on August 13, 2020, from


Scientifically Reviewed
Last updated: 7 Oct 2013
Last reviewed: By John M. Grohol, Psy.D. on 7 Oct 2013
Published on All rights reserved.