Medications for negative symptoms

What are negative symptoms of schizophrenia? 

Negative symptoms are referring to an absence of normal functions. This may include (but is not limited to) blunted affect, which is a scarcity of facial expressions of emotion, reduced frequency and range of gestures and voice modulation, and restricted eye contact; alogia (poverty of speech); asociality (reduced social interaction); avolition (reduced motivation and often poor hygiene) and anhedonia, which is reduced experience of pleasure.

What is the evidence on medications for negative symptoms?

Moderate to high quality evidence finds medium-sized effects of greater improvement in negative symptoms with clozapine, zotepine, amisulpride, olanzapine, perphenazine, and asenapine compared to placebo. There were small improvements over placebo with risperidone, paliperidone, sertindole, chlorpromazine, ziprasidone, aripiprazole, cariprazine, quetiapine, lurasidone, haloperidol, brexpiprazole, and iloperidone. There were no significant differences between placebo and flupentixol or zuclopenthixol.

Moderate quality evidence finds some benefit for improving negative symptoms from second-generation, but not first-generation antipsychotics compared to placebo. Moderate to low quality evidence finds some benefit of antipsychotics plus psychological interventions compared to antipsychotics alone. For individual antipsychotics, amisulpride provided more benefit than placebo; cariprazine, olanzapine and quetiapine provided more benefit than risperidone; olanzapine provided more benefit than haloperidol. Fluphenazine-treated patients received more antiparkinson medication than those on amisulpride or risperidone, risperidone-treated patients received more antiparkinson medication than those on quetiapine, and risperidone produced more extra-pyramidal symptoms than olanzapine.

For other agents, moderate quality evidence finds a small benefit for negative symptoms with adjunctive antidepressants, particularly SNRIs and SSRIs, and with adjunctive glutamatergic agents. Antidepressants were associated with more abdominal pain, constipation, dizziness, and dry mouth than placebo. Moderate to high quality evidence finds a medium-sized improvement in negative symptoms with anti-dementia medications compared to placebo, particularly galantamine, rivastigmine and memantine. There were no differences in adverse events between anti-dementia medications and placebo. Moderate to low quality evidence finds there may also be benefits of other adjunctive agents including aspirin, atomoxetine, celecoxib, cerebrolysin, amotidine, folate, granisetron, insulin, latrepirdine, mazindol, mianserin, mirtazapine, methotrimeprazine, oxytocin, pramipexole, reboxetine, selegiline, sildenafil, sodium benzoate, tropisetron, viloxazine, and vitamin B12.

February 2022

Image: ©Igor Stevanovic –

Last updated at: 12:01 pm, 15th February 2022
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