Original Research

A Review of Psychostimulants for Adults With Depression

Fed Pract. 2015 April;32(suppl 3):30S-37S

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to assess antidepressant response.

This review organized results by stimulant rather than by depression type, even though some studies used > 1 stimulant or recruited patients with different types of depression. Although prevalence, prognosis, and monotherapy differ for unipolar and bipolar depression, psychostimulants target similar symptoms, despite augmenting different monotherapies in unipolar and bipolar depression. Therefore, no distinction is made between assessing studies of stimulants for unipolar and bipolar depression.

Results

A total of 70 articles were identified, and 31 studies met inclusion criteria (Figure). Of the studies included, 12 were double-blind, placebo-controlled (DBPC) trials and 19 were retrospective chart reviews or open studies. Most studies evaluated depression, using validated scales, such as the Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions of Severity, Inventory of Depressive Symptoms, Carroll Depression Rating Scale, Global Assessment of Functioning, Quick Inventory of Depressive Symptomatology, or the Psychiatric Symptom Assessment Scale. Study details are provided in Tables 1 to 4.

Dextroamphetamine and Methylphenidate

Dextroamphetamine and methylphenidate are indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) and exert their effects by inhibiting uptake of norepinephrine and dopamine. ²⁴ In one chart review, patients received dextroamphetamine or methylphenidate augmentation of monoamine oxidase inhibitors (MAOIs) alone or with concurrent tricyclic antidepressants; the majority reported decreased depression. ²⁵ In an openlabel trial, dextroamphetamine was titrated to efficacy in patients who were receiving an MAOI with or without pemoline. ²⁶ Nearly 80% of patients reported long-lasting improvement in depression. In an open-label trial, all patients reported decreased depression when methylphenidate was added to SRIs; however, no scales were used. ²⁷

In a case series, patients with both major depression and persistent depressive disorder (dysthymia) experienced a substantial, quick, and sustained response to dextroamphetamine or methylphenidate augmentation. ²⁸ Addition of lisdexamfetamine significantly reduced depressive symptoms in individuals with inadequate response to escitalopram. ²⁹ Patients with full or partial remission of depression noted improved executive function and residual depressive symptoms after lisdexamfetamine was added to SRI monotherapy. ³⁰ In a trial in which patients received dexamphetamine or methylphenidate as monotherapy or augmentation, 30% to 34% of patients reported mood improvement, but 36% reported no improvement. ³¹ In an extension study, low-dose psychostimulants quickly diminished melancholia. ³²

Methylphenidate was safe and effective in patients with bipolar depression receiving treatment for 1 to 5 years; 44% evidenced significant improvement. ³³ When offered to patients with bipolar depression, patients receiving methylphenidate or dextroamphetamine reported less depression or sedation and did not develop tolerance, mania, or misuse. ³⁴ A case series concluded that methylphenidate addition to mood stabilizers was generally effective and safe. ³⁵

However, not all preparations of methylphenidate have demonstrated efficacy. In one study, osmotic controlledrelease oral system (OROS) methylphenidate improved apathy and fatigue