Augmentation of antidepressants with atypical antipsychotics for treatment-resistant major depressive disorder.
OBJECTIVE
Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment-resistant depression (TRD). This paper will review a biochemical rationale and will summarize the data regarding the effectiveness of AAPs in TRD.


METHODS
Studies were identified using searches of Pubmed/Medline, EMBase and the Cochrane databases by cross-referencing the term 'depression' with each of the six AAPs.


RESULTS
After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia.


CONCLUSIONS
The existing research provides some support for the beneficial effects of AAPs when combined with SSRI's in TRD. These medications pose significant risks that must be considered in their use.
Shelton
Richard C
RC
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA. richard.shelton@vanderbilt.edu
Papakostas
George I
GI
D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000494:pharmacology / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use; D058830:Serotonin 5-HT2 Receptor Antagonists; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D014196:Trazodone / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D065127:Dopamine D2 Receptor Antagonists; D010879:Piperazines; D015363:Quinolones; D058830:Serotonin 5-HT2 Receptor Antagonists; D013844:Thiazoles; D014230:Triazoles; D005473:Fluoxetine; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C051752:nefazodone; C092292:ziprasidone; D000068180:Aripiprazole; D000077152:Olanzapine; D014196:Trazodone