Long‐term effectiveness of oral second‐generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta‐analysis of direct head‐to‐head comparisons

Abstract

Second-generation antipsychotics (SGAs) are recommended for maintenance treatment in schizophrenia. However, comparative long-term effectiveness among SGAs is unclear. Here we provide a systematic review and meta-analysis of randomized trials lasting ≥6 months comparing SGAs head-to-head in schizophrenia and related disorders. The primary outcome was all-cause discontinuation. Secondary outcomes included efficacy and tolerability, i.e., psychopathology, inefficacy-related and intolerability-related discontinuation, relapse, hospitalization, remission, functioning, quality of life, and adverse events. Pooled risk ratio and standardized mean difference were calculated using random-effects models. Across 59 studies (N=45,787), lasting 47.4±32.1 weeks (range 24-186), no consistent superiority of any SGA emerged across efficacy and tolerability outcomes. Regarding all-cause discontinuation, clozapine, olanzapine and risperidone were significantly (p<0.05) superior to several other SGAs, while quetiapine was inferior to several other SGAs. As to psychopathology, clozapine and olanzapine were superior to several other SGAs, while quetiapine and ziprasidone were inferior to several other SGAs. Data for other efficacy outcomes were sparse. Regarding intolerability-related discontinuation, risperidone was superior and clozapine was inferior to several other SGAs. Concerning weight gain, olanzapine was worse than all other compared non-clozapine SGAs, and risperidone was significantly worse than several other SGAs. As to prolactin increase, risperidone and amisulpride were significantly worse than several other SGAs. Regarding parkinsonism, olanzapine was superior to risperidone, without significant differences pertaining to akathisia. Concerning sedation and somnolence, clozapine and quetiapine were significantly worse than some other SGAs. In summary, different long-term SGA efficacy and tolerability patterns emerged. The long-term risk-benefit profiles of specific SGAs need to be tailored to individual patients to optimize maintenance treatment outcomes.

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

“…However, the evidence of this effect is contradictory since there is also proof of the decrease during the consumption of this drug. It has been reported that according to the period of consumption, the effects on PRL blood levels change (111,198,199): The consumption during short periods (<2 weeks) or the intake of a single dose does not alter PRL levels (111,200).…”

How do we select an antipsychotic for those with schizophrenia?

“…Of 20 antipsychotic medications that significantly lowered discontinuation rates compared with placebo, amisulpride, olanzapine, paliperidone, and clozapine were amongst those with the lowest rates of all-cause discontinuation, whereas haloperidol was the highest [6]. Focusing exclusively on direct comparisons of SGAs, a separate meta-analysis supported these findings, identifying clozapine, olanzapine, and risperidone as superior to several other SGAs, whereas quetiapine was inferior to several [12].…”

“…The bulk of evidence from meta-analyses on antipsychotic medications have established three 'tiers' of efficacy: 1) clozapine has consistently demonstrated superiority over other treatment options, 2) olanzapine, risperidone, and amisulpride are significantly more efficacious than FGAs and most other SGAs, and 3) the remaining antipsychotics are similarly efficacious [5,6,12]. Some evidence suggests that quetiapine and ziprasidone may be inferior to some other SGAs, though quetiapine is often under dosed due to sedation [12].…”

“…Although side effect differences between individual antipsychotics are very apparent, efficacy differences are more subtle. Tiers of efficacy have emerged, with clozapine showing the most efficacy, followed by olanzapine, risperidone, and amisulpride, followed then by all remaining antipsychotic medications [5,6,12]. To maximize quality of life, some patients may be willing to live with varying side effects if the trade-off is a greater reduction in psychopathology.…”

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities

“…1 Dopamine modulating antipsychotics remain the primary and only currently approved treatment for schizophrenia, and over the past years many different antipsychotics have been developed and tested for their efficacy and safety in reducing acute symptoms of schizophrenia and maintaining stability. [5][6][7][8][9] However, currently available drugs are mostly effective against positive symptoms (i.e., hallucinations, delusions, disorganized thought or speech, and bizarre behaviors). This situation leaves most patients with diverse residual symptoms relatively untreated, especially negative symptoms (lack of motivation, drive, enjoyment, social interactions) and cognitive dysfunction (deficits in attention, memory, executive functioning, grasp of social situations/interactions), which lead to poor quality of life outcomes and lifelong impairments, [10][11][12][13][14][15][16][17][18] as cognitive and negative symptoms persist for most of the patients' lives.…”