Antidepressants are widely used in schizophrenia because dysphoria and depressive symptoms are common problems for patients. Although antidepressants seem like a good idea in this clinical scenario, their usefulness has never been clearly established. Much of the literature on antidepressants for schizophrenia stems from the era of first-generation antipsychotics and tricyclic antidepressants. The older literature suggests that tricyclic antidepressants added during an acute psychotic symptom exacerbation will in fact impede resolution of psychosis, whereas postpsychotic depressive episodes are helped with antidepressants, and some patients will relapse if antidepressants are discontinued. This field of inquiry is hampered by a high placebo-response rate to antidepressants, 50% in one study that compared sertraline with placebo in patients with remitted schizophrenia who had a depressive episode (Addington et al., 2002).

There is a small literature that selective serotonin reuptake inhibitors (SSRIs) can be a useful adjunct to treat negative symptoms (Rummel et al., 2005). The effect size is small, and I am unsure if you can truly see a clinical difference in most patients. Nevertheless, given the lack of good treatment options, a time-limited trial can be justified.

Recently, mirtazapine has been shown in a controlled trial to be rather effective for akathisia. Remember to follow a patient’s weight if you prescribe mirtazapine for long-term use.

Most psychiatrists who treat many patients with schizophrenia will agree with me that benzodiazepines are a very useful medication class for adjunctive use in patients with schizophrenia, both during the acute treatment phase and the chronic phase, even though very few pharmacology trials have been conducted. Table 15.1 gives indications for which a benzodiazepine could be considered. Note that benzodiazepines are a first-line treatment for catatonia. When you use benzodiazepines, keep in mind the possibility of impairing cognition (but also the deleterious effects of untreated anxiety on performance).

One of the few controlled trials of benzodiazepines for the treatment of schizophrenia found adding the benzodiazepine diazepam as effective as increasing the antipsychotic fluphenazine, in the case of the study, to stave off a psychotic relapse (Carpenter et al., 1999).