Stimulants for depression: On the up and up?

Abstract

The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression--specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants. More importantly, there is little evidence from randomised controlled trials supporting their efficacy in treating depression, although modafinil has been shown to be effective in reducing prominent depressive symptoms, such as fatigue. Research is urgently required to clarify psychostimulants' mechanisms of action and to evaluate their long-term benefits and risks in the treatment of major and bipolar depression. Ultimately, specificity of action needs to be determined to inform the sophisticated clinical use of psychostimulants in the management of depression. Until then they should only be prescribed if absolutely necessary, and even then their prescription should be facilitatory and time limited unless it is for investigational purposes.

Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force

“…Pro‐dopaminergic drugs such as pramipexole and modafinil should be investigated in an adjunctive design given some concern about potential risk of mania switch . Such trials should ideally restrict recruitment to euthymic patients, given the antidepressant effects of these compounds, which would confound the interpretation of potential cognitive benefits in symptomatic patients.…”

Reduced positive emotion and underarousal are uniquely associated with subclinical depression symptoms: Evidence from psychophysiology, self‐report, and symptom clusters

“…Such interventions may also ameliorate the psychomotor slowing and lack of energy that are symptoms of underarousal in depression (Salamone, Correa, Mingote, Weber, & Farrar, 2006). Conversely, stimulant-like drugs (but not traditional psychostimulant medications) show promise in treating the fatigue and sleepiness specifically that are implicated in depressive underarousal (Malhi et al, 2016). Such drugs may ameliorate patterns of cortical activity in depression that are consistent with both underarousal and low positive emotionality (Bruder et al, 1997).…”

Right care, first time: a highly personalised and measurement‐based care model to manage youth mental health

“…While preliminary, there is evidence from an open label trial demonstrating that resolution of depressive symptoms in individuals with a circadian‐type depressive phenotype is strongly correlated with the correction of abnormal underlying circadian parameters (specifically, laboratory‐determined dim‐light melatonin onset times) . A second line pharmacological approach could include mood‐stabilising medications such as lithium, pregabalin and lamotrigine or stimulant drugs such as modafinil …”