We undertook a systematic review, searching PubMed/Scopus/Clinicaltrials.gov for double-blind, randomized, placebo-controlled studies of psychostimulants or
atomoxetine in
schizophrenia published up to 1 January 2017. A meta-analysis of outcomes reported in two or more studies is presented.
RESULTS: We included 22 studies investigating
therapeutic effects of stimulants (k=14) or measuring symptomatic worsening/relapse prediction after stimulant challenge (k=6). Six studies of these two groups plus one additional study investigated biological effects of psychostimulants or
atomoxetine. No effect resulted from interventional studies on
weight loss (k=1), smoking cessation (k=1), and positive symptoms (k=12), and no improvement was reported with
atomoxetine (k=3) for negative symptoms, with equivocal findings for negative (k=6) and mood symptoms (k=2) with
amphetamines. Attention, processing speed, working memory, problem solving, and executive functions, among others, showed from no to some improvement with
atomoxetine (k=3) or
amphetamines (k=6). Meta-analysis did not confirm any effect of stimulants in any symptom domain, including negative symptoms, apart from
atomoxetine improving problem solving (k=2, standardized mean difference (SMD)=0.73, 95% CI=0.10-1.36, p=0.02, I2=0%), and trending toward significant improvement in executive functions with
amphetamines (k=2, SMD=0.80, 95% CI=-1.68 to +0.08, p=0.08, I2=66%). In challenge studies,
amphetamines (k=1) did not worsen symptoms, and
methylphenidate (k=5) consistently worsened or predicted relapse. Biological effects of
atomoxetine (k=1) and
amphetamines (k=1) were cortical activation, without change in β-
endorphin (k=1), improved response to
antipsychotics after
amphetamine challenge (k=2), and an increase of
growth hormone-mediated
psychosis with
methylphenidate (k=2). No major side effects were reported (k=6).
CONCLUSIONS: