04. Depression in Schizophrenia

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For our next Quick Take, let’s look at the challenge of depression and depressive symptoms in people with schizophrenia.

This is a big problem. Twenty-five percent of patients with schizophrenia, according to one study, meet DSM criteria for depression, and 50% have significant depression symptoms. And since anhedonia can amplify the amotivation that’s part of the schizophrenia complex, and social withdrawal can drastically lower quality of life, we really need to look at this depression issue.

First of all, let’s divide depression into the depression that’s associated with acute psychosis. That’s kind of easy because the guidelines for this are very consistent in suggesting that this acute phase depression be managed simply by targeting resolution of the psychosis. For depression that’s associated with acute psychotic schizophrenia, treat the psychosis. The big problem is depression that continues after that.

We’re going to look here at a new study from France that examines 10 guidelines on how to manage depression in schizophrenia focusing on depression that continues after resolution of acute psychosis. The bad news is, there’s not much here in these 10 guidelines that you haven’t really already taken into consideration when you’re faced with depression in the context of schizophrenia. It’s antidepressants versus psychotherapy versus switching to a different antipsychotic—particularly switching to a second-generation antipsychotic if you’re not already there.

Which of these strategies is better? Again, we’re looking at 10 guidelines pooled together into a single review by Drs. Donde and Vignaud and colleagues from France. The guidelines all include psychotherapy as well as antidepressants. But only 1 of these guidelines is algorithmic in the sense of “first you should do this, then you should do that.” That’s the Australian set of guidelines. And they suggest the psychotherapeutic intervention first, then switching from a first-generation to second-generation antipsychotic if you aren’t already there, and then finally after that, consider adding an antidepressant. One guideline also includes lithium in that antidepressant role, but the data are very mixed on efficacy there.

Which psychotherapies? According to the Australian guidelines, the ones that are mentioned are psychoeducation, vocational rehabilitation, stress management, problem solving, peer support, and supportive psychotherapy. These are not examined independent of one another in terms of how to rank-order them, and only 1 guideline broke them out separately as opposed to just referring to psychotherapy in general. If you do come around to adding an antidepressant in that third step in this process, the guidelines—again, taken together in this French review—point out the risk of drug-drug interactions with akathisia that can be worsened by an SSRI or SNRI; weight gain and sedation that can increase with add-on mirtazapine or lithium; that bupropion may lower the epileptic threshold and induce seizures; and finally that antidepressants can increase the risk of QT prolongation on the electrocardiogram. Obviously, one of those would be citalopram.

I’m going to take a brief tangent here about akathisia, and then we’ll summarize the findings from this review of guidelines. Remember that akathisia was quite prominent on this list as a potential exacerbation by antidepressants. I would like us all to consider, what is the akathisia that’s associated with antidepressants? Is it really the akathisia that we associate with dopamine antagonists? There is a serotonergic connection between the raphe nuclei and the dopaminergic striatal region. It’s kind of complicated, but there’s no question that at least sertraline, which is somewhat more directly dopaminergic, can cause movement disorders. There is a remarkable case of hemichorea that remitted when sertraline was discontinued, and there’s a video for that, which I’ll include in the references. So, if you ever wondered, is it really true that antidepressants can just cause plain old akathisia, there is a classic example.

But I’d also like to invite us all to remember that mixed states that can be induced by antidepressants can include an extreme agitation and motor hyperactivity that can look like akathisia and feel like restlessness. So, when you see that, just be vigilant for the possibility that what looks like akathisia with an antidepressant could actually be an exacerbation of a bipolar or schizoaffective component in this psychotic illness that just *looks like* schizophrenia and is being made worse by the antidepressant. That’s the end of my little tangent on akathisia.

In summary of the review of 10 international guidelines on the treatment of depression in schizophrenia, there are 2 main points. First, don’t forget to look for it after psychosis is resolved. It’s prevalent, and it lowers quality of life. And secondly, these are potentially treatable depressive symptoms, and they should be approached with psychotherapy, second-generation antipsychotics, and then, if you are forced into it, antidepressants.

Abstract

Management of Depression in Patients With Schizophrenia Spectrum Disorders: A Critical Review of International Guidelines

C. Dondé, P. Vignaud, E. Poulet, J. Brunelin, F. Haesebaert

Objectives: Depression is a frequent but potentially treatable clinical dimension in patients with schizophrenia spectrum disorders (PWS). However, there is a lack of consensual recommendations regarding the optimal strategy to manage depression in PWS. In this study, we aimed to compare the various proposed strategies to define a core set of valid care recommendations for depression management in PWS.

Methods: After a systematic search of the literature, the methodological quality of 10 international guidelines from four continents was compared using a validated guideline appraisal instrument (AGREE II). Key recommendations for the management of depression in PWS were subsequently reviewed and discussed.

Results; The methodological quality of the guidelines was heterogeneous. Although all guidelines proposed pharmacotherapy, psychosocial interventions were a minor concern. Waiting for antipsychotic effects mostly was recommended during the acute phase of schizophrenia. During the postpsychotic phase of the illness, a switch to a second‐generation antipsychotic and/or the adjunction of an antidepressant were the primary recommendations. Cognitive behavioural therapy and other medications were considered with strong variations.

Conclusions: Further studies are needed to strengthen the level of evidence for antidepressive approaches in PWS. The inclusion of PWS as stakeholders is also considered to be a major issue for future guideline development.

Reference

Dondé, C., Vignaud, P., Poulet, E., Brunelin, J., & Haesebaert, F. (2018). Management of depression in patients with schizophrenia spectrum disorders: A critical review of international guidelines. Acta Psychiatrica Scandinavica, 138(4), 289-299.