Do the old psychostimulant drugs have a role in managing treatment-resistant depression?

Acta Psychiatr Scand. 2010 Apr;121(4):308-14. doi: 10.1111/j.1600-0447.2009.01434.x. Epub 2009 Jul 9.


Objective: As the authors have observed clinical benefit from the psychostimulants methylphenidate and dexamphetamine for treating resistant melancholic and bipolar depression, those drugs were evaluated in a consecutively recruited sample of 50 such patients.

Method: Patients (27 bipolar, 23 unipolar) received either methylphenidate (n = 44) or dexamphetamine (n = 6), with 30 having it prescribed as an augmenting drug and 20 as monotherapy. At the final review, ranging from 6 weeks to 62 months (mean 57 weeks), 52% were still receiving their psychostimulant.

Results: Thirty-four per cent reported the psychostimulant as distinctly improving their depression, 30% reported some level of improvement and 36% reported no improvement and/or side-effects. For improvers, the modal dose of methylphenidate was 20 mg. Significant side-effects were reported by 18% (including one manic response), switching was rare and limited to the bipolar subjects, and most side-effects were minor. Any positive response occurred rapidly and loss of efficacy was rare. Testing of tricyclic levels in some patients suggested that stimulant drugs may raise tricyclic levels in those who are rapid metabolizers.

Conclusion: Although this study was not controlled, the high success rate in a diagnostically refined sample implies that the psychostimulants may be efficacious for patients with melancholic and bipolar depression who have failed to respond to orthodox antidepressant drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / blood
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / epidemiology
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / epidemiology
  • Dextroamphetamine / adverse effects
  • Dextroamphetamine / therapeutic use*
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methylphenidate / adverse effects
  • Methylphenidate / therapeutic use*
  • Middle Aged
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Central Nervous System Stimulants
  • Methylphenidate
  • Dextroamphetamine