Adjunct Mirtazapine for Negative Symptoms of Schizophrenia

Abstract

Negative symptoms of schizophrenia are characterized by affective flattening, alogia, avolition, and anhedonia and are often nonresponsive to antipsychotic therapy. Because negative symptoms are predictive of poor occupational and social functioning, as well as poor global outcomes, numerous studies evaluating adjunct therapy to antipsychotics have been conducted. This review focuses on the use of the antidepressant mirtazapine as adjunct therapy to antipsychotics for the treatment of negative symptoms of schizophrenia. A literature search of the MEDLINE database (from inception-March 2011) identified eight relevant articles: six were randomized, double-blind, placebo-controlled trials, and two were open-label trials. Of the six randomized trials reviewed, four studies assessed add-on mirtazapine to second-generation antipsychotics, whereas two studies examined add-on mirtazapine to first-generation antipsychotics. Five of the six randomized trials supported the use of mirtazapine for negative symptoms of schizophrenia. Of the two open-label trials, one naturalistic study demonstrated that mirtazapine add-on therapy to clozapine was not associated with improvements in negative symptoms; however, this study focused primarily on improvements in cognition, not negative symptoms. An open-label extension phase to a randomized controlled trial showed that mirtazapine continued to produce significant improvement in negative symptoms over a longer duration of time, when added to first-generation antipsychotic therapy. Overall, mirtazapine appears to be well tolerated and associated with few drug interactions. Although adjunct mirtazapine to antipsychotics has been shown to be effective at doses of 30 mg/day in most of the trials, limitations of these studies include short study duration and small sample sizes. To improve generalizability, larger multicenter studies with broader inclusion criteria should be conducted. In addition, studies of longer duration that use different mirtazapine dosages are needed to further assess the benefits of mirtazapine for negative symptoms of schizophrenia.

Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

“…Although probably effective as an add-on medication for schizophrenia (Phan and Kreys, 2011), mirtazapine apparently increases body weight and level of cholesterol -both proven to be cardiovascular disease risk factors. Thus, a clinician should carefully weight these pros and cons when considering mirtazapine add-on treatment in each particular case.…”

“…Mirtazapine, one of the few existing receptor-blocking antidepressants with a specific psychopharmacological profile, seems to boost the desirable effects of the FGAs on the negative, positive and cognitive symptoms of schizophrenia (Joffe et al 2009 ;Stenberg et al 2010 ;Terevnikov et al 2010 ;Phan and Kreys, 2011). Mirtazapine also causes weight gain and dyslipidaemia in patients with major depressive disorder (MDD ; Laimer et al 2006).…”

A biopsychosocial evaluation of the risk for suicide in schizophrenia

“…2 Individuals with SCZ generally experience a range of symptoms, such as delusions, sensory hallucinations, flat or blunted emotions, and disorganized thoughts and speech. 3 These symptoms may be associated with an increased risk for self-injurious and suicidal behaviors. 2 In particular, suicide attempts and suicide completion are among the largest contributors to the increased morbidity and mortality rates in SCZ.…”

Add-on clinical effects of selective antagonist of 5HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study

“…Over the last several years, researchers have repeatedly tried to find a way to expand the profile of therapeutic action of antipsychotics through pharmacological agents complimentary to treatment targets other than the dopaminergic system. [15][16][17][18][19][20][21][22][23][24][25][26][27] Hypotheses about the role of the serotonin system in the development of various mental disorders [28][29][30][31] continue to be relevant. Of recent special interest is one of the serotonergic system structures-the type 6 serotonergic receptors , which are localized primarily in the central nervous system (CNS), particularly in the limbic region.…”

“…Over the last several years, researchers have repeatedly tried to find a way to expand the profile of therapeutic action of antipsychotics through pharmacological agents complimentary to treatment targets other than the dopaminergic system 15 – 27 . Hypotheses about the role of the serotonin system in the development of various mental disorders 28 – 31 continue to be relevant.…”