Original Research

A Review of Psychostimulants for Adults With Depression

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References

as the development of dependence or misuse. Urine toxicology testing is recommended for dextroamphetamine and methylphenidate to screen for adherence and diversion.

Limitations

Using only PubMed and MEDLINE databases limited the search to articles published in English after 1985, excluding letters and case reports to identify studies with higher evidence (the studies were not weighted based on study design). In addition, the studies had certain limitations. These include a limited number of DBPC trials, most were of short duration. It is also difficult to compare studies due to various rating scales used and concurrent
medication regimens of study subjects. These limitations raise questions surrounding the long-term efficacy of stimulants, and there is no consensus for how long a stimulant should be continued if beneficial. Longer, higherpowered, DBPC trials are warranted to determine longterm efficacy and safety of stimulant augmentation. 62

Conclusion

For patients with depression who have not responded to other augmentation strategies, psychostimulants may be offered to improve mood, energy, and concentration. For clinicians considering stimulant augmentation, modafinil and armodafinil are reasonable choices given their efficacy in double-blind, placebo-controlled trials and lower risk of misuse. Dextroamphetamine (particularly lisdexamphetamine) and methylphenidate may be appropriate for patients who have not benefited from or tolerated modafinil or armodafinil, provided these patients do not have a medical history of cardiac disease or current substance use.

Osmotic controlled-release oral system methylphenidate seems to be ineffective as an augmenting agent. The efficacy of atomoxetine for augmentation is questionable, but atomoxetine could be offered if other stimulants were contraindicated, ineffective, or poorly tolerated. Both OROS methylphenidate and atomoxetine should be evaluated in additional trials before they can be recommended as augmentation therapies. Certain psychostimulants may be appropriate and reasonable adjunctive pharmacotherapies for patients with unipolar or bipolar depression who have failed other augmentation strategies, for patients who have significant fatigue or cognitive complaints, or for elderly patients with melancholic or somatic features of depression.

Acknowledgements
The authors thank Maureen Humphrey-Shelton and Kathy Thomas for their help in obtaining references .

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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