title: Somatic augmentation strategies in clozapine resistance--what facts?
abstract: BACKGROUND
  Polypharmacy without evidence-based support is sometimes needed for patients treated with 40% to 70% clozapine who are clozapine nonresponders. Several somatic augmentation strategies are proposed in the scientific literature, with different levels of evidence for safety and efficacy.
  
  
  OBJECTIVE
  The purpose of the present study is to review the available literature on the efficacy and safety of clozapine augmentation with somatic agents other than antipsychotics. The following classes of agents are considered: (1) mood stabilizers, (2) antidepressants, (3) electroconvulsive therapy and repetitive transcranial magnetic stimulation, (4) glutamatergic agents, (5)fatty acids supplements, and (6) benzodiazepines.
  
  
  RESULTS
  Case controls and small-size clinical trials largely dominate the literature, limiting the power to draw conclusions concerning safety issues and the meaning of negative studies. Moreover, variable definitions of clozapine resistance, heterogeneous outcome measures, and short duration of treatment trials are additional limitations.
  
  
  CONCLUSIONS
  Generally, adjunctive strategies for clozapine-resistant patients remain based on scarce evidence of efficacy and significant safety concerns. Low-frequency repetitive transcranial magnetic stimulation, fatty acids supplements, and mirtazapine showed good tolerability and some efficacy, but the results need replication.
authors.affiliation: Psychiatry Department, University of Montreal Montréal, Québec, Canada. constantin.tranulis@gmail.com
authors.forename: Constantin
authors.initials: C
authors.lastname: Tranulis
authors.forename: Fayçal
authors.initials: F
authors.lastname: Mouaffak
authors.forename: Laurent
authors.initials: L
authors.lastname: Chouchana
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stip
authors.forename: Raphael
authors.initials: R
authors.lastname: Gourevitch
authors.forename: Marie France
authors.initials: MF
authors.lastname: Poirier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Olié
authors.forename: Henri
authors.initials: H
authors.lastname: Lôo
authors.forename: David
authors.initials: D
authors.lastname: Gourion
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003024:Clozapine / Q000627:therapeutic use*; D004351:Drug Resistance; D004357:Drug Synergism; D004565:Electroconvulsive Therapy; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D019338:Polypharmacy; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003024:Clozapine