Review: Combination therapy with non-clozapine atypical antipsychotic medication: a review of current evidence

Abstract

Use of combined antipsychotics for patients with treatment-resistant/refractory schizophrenia is common practice in psychiatry. The objective of this paper is to review the current literature on combining non-clozapine atypical antipsychotics as well as discussing the theoretical benefits and risks, and summarizing the implications for clinical practice. We found in cases of treatment-resistant schizophrenia, where clozapine is deemed inappropriate, combination therapy with non-clozapine atypical antipsychotics is a strategy worthy of consideration. Combinations using olanzapine with either amisulpride or risperidone--or quetiapine with risperidone--in theory act on different receptor profiles and in the limited data available have shown improvement in symptoms, been used most frequently, and on balance have more data on safety. Initial case reports suggest that aripiprazole combined with non-clozapine atypicals may worsen psychosis. The current literature, however, has significant limitations. For this reason, due to the lack of data on safety, caution is recommended. There needs to be further well-designed studies with the aim to specifically investigate the effects of combination therapy to allow the clinician to better balance the risks and benefits (both clinical and economical) of treatment.

Long-Term Efficacy and Tolerability of Clozapine Combined with Ziprasidone or Risperidone

“…The most common approaches involve olanzapine [42] and clozapine [9,30,43] . These strategies rest upon the neurobiological strategy to specifically replenish the receptor interaction profi le, for example, by means of a subsidiary dopamine receptor interaction after add-on of sulpiride [32] , amisulpride [6,27] or aripiprazole [10,13] .…”

“…Withdrawal of consent (N = 2) 9. insuffi cient treatment response (N = 2) and therefore switched to CZ (N = 2) follow-up 2 (52 weeks) 7 no dropouts 4.…”

Augmentation of atypical antipsychotics with valproic acid. An open‐label study for most difficult patients with schizophrenia

“…Examples include augmentation with other psychotropics (Leucht et al, 2007a;Leucht et al, 2007b;Volz et al, 2007) including valproate (Schwarz et al, 2008) and polypharmacy using another antipsychotic (Chan and Sweeting, 2007;Paton et al, 2007). Specifically, there have been some positive reports on augmentation of atypical antipsychotics with valproate (Casey et al, 2003;Citrome et al, 2004), although the results are not necessarily consistent (Citrome et al, 2007;Casey et al, 2009).…”

Aripiprazole for the Management of Olanzapine-induced Weight Gain

“…In particular, olanzapine seems to be prone to metabolic side eff ects [10] . This dibenzodiazepine has been used in combination with other atypical antipsychotics in cases of treatment resistant psychoses [2,11] . In order to counteract hyperprolactinemia, treatment resistant negative symptoms and metabolic adversity the combination of olanzapine with aripiprazole, a partial dopamine and serotonin receptor agonist [7] , has been applied, quite in parallel to experiences with clozapine and aripiprazole [5] .…”