Aripiprazole in the Treatment of Depressive and Anxiety Disorders

A Review of Current Evidence

Abstract

Despite the availability of different classes of drugs for the treatment of depressive and anxiety disorders, there are a number of clinically significant unmet needs, such as a high prevalence of treatment resistance, partial response, subsyndromal symptomatology, recurrence and relapse. With the approval of atypical antipsychotics, which are associated with a lower adverse effect burden than typical antipsychotics, consideration of their off-label use for the treatment of affective disorders and various other psychiatric disorders has become a viable option. However, consideration should be given to the US FDA black box warning indicating that atypical antipsychotics may increase mortality risk, particularly in the elderly population with dementia-related psychosis.

There has been much conjecture about the utility of these atypical drugs to facilitate traditional antidepressant therapy, either in combination (from the initiation of therapy) or as adjunctive therapy (in the case of partial/incomplete response). Nevertheless, at present, available evidence from randomized, placebo-controlled trials is sparse, and a formal risk/benefit assessment of the use of these agents in a nonpsychotic patient population is not yet possible.

As a representative agent from the atypical antipsychotic class with a novel mechanism of action and a relatively low adverse effect burden, aripiprazole represents an interesting potential treatment for depressive and anxiety disorders. In this review, we focus on the rationale for the use of aripiprazole in these disorders.

Preclinical data suggests that aripiprazole has a number of possible mechanisms of action that may be important in the treatment of depressive and anxiety disorders. Such mechanisms include aripiprazole action at serotonin (5-HT) receptors as a 5-HT1a partial receptor agonist, a 5-HT2C partial receptor agonist and a 5-HT2a receptor antagonist. Aripiprazole also acts as a dopamine D2 partial receptor agonist, and has a possible action at adrenergic receptors. Furthermore, aripiprazole may have possible neuroprotective effects.

Clinical studies demonstrate that aripiprazole may be useful in the treatment of bipolar depression, major depressive disorder, treatment-resistant depression and possibly anxiety disorders. Clinical data also suggest that aripiprazole may have a lower adverse effect burden than the other atypical drugs.

Future research may confirm the potential utility of aripiprazole in the treatment of depressive and anxiety disorders.

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Acknowledgements

The authors received no financial support to prepare this review and have no conflicts of interest directly relevant to its contents.

Dr Pae has received research grants from the Korean divisions of GlaxoSmithKline, AstraZeneca, Janssen Pharmaceuticals, Eli Lilly and Company, Otsuka, Wyeth Pharmaceuticals, the Korean Research Foundation and the Korean Institute of Science and Technology Evaluation and Planning; and has received honoraria and is on the speaker’s bureaus of the Korean divisions of GlaxoSmithKline, Lundbeck, AstraZeneca, Janssen Pharmaceuticals, Eli Lilly and Company, McNeil Consumer and Specialty Inc. and Otsuka.

Dr Patkar is a consultant for Bristol-Myers Squibb, GlaxoSmithKline and Reckitt Benckiser; is on the speaker’s bureau of Bristol-Myers Squibb, GlaxoSmithKline and Reckitt Benckiser; and has received research support from National Institutes of Health, AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen, McNeil Consumer and Specialty Inc., Organon, Jazz Pharmaceuticals and Pfizer Inc.

Dr Masand is a consultant for Bristol-Myers Squibb Company, Cephalon Inc., Eli Lilly and Company, Forest Laboratories Inc., GlaxoSmithKline, i3CME, Janssen Pharmaceutica, Jazz Pharmaceuticals, Organon, Pfizer Inc., Targacept Inc. and Wyeth Pharmaceuticals; is on the speaker’s bureau of AstraZeneca, Bristol-Myers Squibb Company, Forest laboratories Inc., GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc., and Wyeth Pharmaceuticals; and has received research support from AstraZeneca, Bristol-Myers Squibb Company, Cephalon Inc., Eli Lilly and Company, Forest laboratories Inc., GlaxoSmithKline, Ortho McNeil Pharmaceutical, Inc., Janssen Pharmaceuticals and Wyeth Pharmaceuticals.

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Pae, CU., Serretti, A., Patkar, A.A. et al. Aripiprazole in the Treatment of Depressive and Anxiety Disorders. CNS Drugs 22, 367–388 (2008). https://doi.org/10.2165/00023210-200822050-00002

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Keywords

  • Major Depressive Disorder
  • Anxiety Disorder
  • Aripiprazole
  • Ziprasidone
  • Major Depressive Disorder Patient