Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Second-generation antipsychotics

15 evidence topics · 13 sources

APA practice guideline: antipsychotic treatment and continuation

“APA recommends (1A) that patients with schizophrenia be treated with an antipsychotic medication and monitored for effectiveness and side effects.” (opens the source at this quote in a new tab)
“APA recommends (1A) that patients with schizophrenia whose symptoms have improved with an antipsychotic medication continue to be treated with an antipsychotic medication.” (opens the source at this quote in a new tab)
“APA suggests (2B) that patients with schizophrenia whose symptoms have improved with an antipsychotic medication continue to be treated with the same antipsychotic medication.” (opens the source at this quote in a new tab)

APA practice guideline: no ranking of agents and no preference between generations

“An evidence-based ranking of FGAs and SGAs or an algorithmic approach to antipsychotic selection is not possible because of the significant heterogeneity in clinical trial designs, the limited numbers of head-to-head comparisons of antipsychotic medications, and the limited clinical trial data for a number of the antipsychotic medications.” (opens the source at this quote in a new tab)
“By the same token, it is not possible to note a preference for either SGAs or FGAs.” (opens the source at this quote in a new tab)
“there is no definitive evidence that one antipsychotic will have consistently superior efficacy compared with another, with the possible exception of clozapine.” (opens the source at this quote in a new tab)
“Furthermore, there is no reliable strategy to predict response or risk of side effects with one agent compared with another.” (opens the source at this quote in a new tab)

VA/DoD guideline: acute treatment, maintenance treatment, and switching

“We recommend the use of an antipsychotic medication other than clozapine for the treatment of an acute episode in individuals with schizophrenia or first-episode psychosis who have previously responded to antipsychotic medications.” (opens the source at this quote in a new tab)
“We recommend the use of an antipsychotic medication for the maintenance treatment of schizophrenia to prevent relapse and hospitalization in individuals with schizophrenia who have responded to treatment.” (opens the source at this quote in a new tab)
“Choice of antipsychotic medication should be based on an individualized evaluation that considers patient-specific characteristics and side effect profiles of the different antipsychotic medications.” (opens the source at this quote in a new tab)
“We suggest a trial of another antipsychotic medication for individuals with schizophrenia who do not respond to (or tolerate) an adequate trial of an antipsychotic medication.” (opens the source at this quote in a new tab)

VA/DoD guideline: adverse effect profile of second-generation agents

“In contrast, second-generation antipsychotic medications (SGA) (e.g., olanzapine, quetiapine, risperidone) are less likely than FGAs to cause EPS but might be associated with increased risk of weight gain and other metabolic abnormalities, including hyperlipidemias and type 2 diabetes mellitus.” (opens the source at this quote in a new tab)
“Finally, both FGAs and SGAs might cause cardiovascular side effects, including dysrhythmias and QT prolongation, and, rarely, seizures.” (opens the source at this quote in a new tab)

NICE guideline: oral antipsychotic medication with psychological interventions

“For people with an acute exacerbation or recurrence of psychosis or schizophrenia, offer: oral antipsychotic medication (see the section on how to use antipsychotic medication) in conjunction with psychological interventions (family intervention and individual CBT, delivered as described in the section on how to deliver psychological interventions).” (opens the source at this quote in a new tab)
“The choice of antipsychotic medication should be made by the service user and healthcare professional together, taking into account the views of the carer if the service user agrees.” (opens the source at this quote in a new tab)
“Do not initiate regular combined antipsychotic medication, except for short periods (for example, when changing medication).” (opens the source at this quote in a new tab)

INTEGRATE international algorithm: development and key recommendations

“From May 1, 2023, to Jan 1, 2025, International Guidelines for Algorithmic Treatment (INTEGRATE) authors from all UN regions collaborated to develop a consensus guideline focused on the pharmacological treatment of schizophrenia.” (opens the source at this quote in a new tab)
“Key recommendations include a focus on metabolic health from treatment initiation, timely assessment and management of non-response, symptom domain-specific interventions, mitigation of side-effects, and the prompt use of clozapine in cases of treatment resistance.” (opens the source at this quote in a new tab)

Australian and New Zealand GRADE guideline: first-line and second-line agents

“We recommend that people with schizophrenia should be given oral second-generation antipsychotic medications with a favourable cardiometabolic side effect (including hyperprolactinemia) profile as the first-line treatment (i.e. aripiprazole, brexiprazole, cariprazine, lurasidone).” (opens the source at this quote in a new tab)
“Combined, we recommend choosing the second antipsychotic medication from the remaining agents from the first-line treatment options (aripiprazole, brexpiprazole, cariprazine, or lurasidone) with additional consideration for agents with different receptor profiles such as amisulpride and risperidone” (opens the source at this quote in a new tab)

Acute efficacy against placebo: 167 trials over sixty years

“The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants.” (opens the source at this quote in a new tab)
“The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38.” (opens the source at this quote in a new tab)
“Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27).” (opens the source at this quote in a new tab)
“Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response.” (opens the source at this quote in a new tab)

Comparative acute efficacy of 32 oral antipsychotics: network meta-analysis

“We identified 54 417 citations and included 402 studies with data for 53 463 participants.” (opens the source at this quote in a new tab)
“Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from −0·89 (95% CrI −1·08 to −0·71) for clozapine to −0·03 (−0·59 to 0·52) for levomepromazine (40 815 participants).” (opens the source at this quote in a new tab)
“Clozapine, amisulpride, zotepine, olanzapine, and risperidone reduced overall symptoms significantly more than many other drugs” (opens the source at this quote in a new tab)
“There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete.” (opens the source at this quote in a new tab)

Comparative adverse effects of 32 oral antipsychotics: network meta-analysis

“Mean differences compared to placebo for weight gain (28 317 participants) ranged from −0·16 kg (−0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from −77·05 ng/mL (−120·23 to −33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from −2·21 ms (−4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole).” (opens the source at this quote in a new tab)
“Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide).” (opens the source at this quote in a new tab)
“Olanzapine, asenapine, lurasidone, sertindole, haloperidol, amisulpride, risperidone, and paliperidone were associated with significantly elevated prolactin levels (mean difference range 4·47–48·51 ng/mL).” (opens the source at this quote in a new tab)

Metabolic effects of 18 antipsychotics: network meta-analysis

“Of 6532 citations, we included 100 randomised controlled trials, including 25 952 patients.” (opens the source at this quote in a new tab)
“Mean differences for weight gain compared with placebo ranged from −0·23 kg (95% CI −0·83 to 0·36) for haloperidol to 3·01 kg (1·78 to 4·24) for clozapine” (opens the source at this quote in a new tab)
“Marked differences exist between antipsychotics in terms of metabolic side-effects, with olanzapine and clozapine exhibiting the worst profiles and aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone the most benign profiles.” (opens the source at this quote in a new tab)

Maintenance treatment: network meta-analysis of 32 oral and long-acting injectable antipsychotics

“All antipsychotics had risk ratios (RRs) less than 1·00 when compared with placebo for relapse prevention and almost all had 95% credible intervals (CrIs) excluding no effect.” (opens the source at this quote in a new tab)
“As we found no clear differences between antipsychotics for relapse prevention, we conclude that the choice of antipsychotic for maintenance treatment should be guided mainly by their tolerability.” (opens the source at this quote in a new tab)

Long-term head-to-head comparisons of oral second-generation antipsychotics

“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.” (opens the source at this quote in a new tab)
“Concerning weight gain, olanzapine was worse than all other compared non‐clozapine SGAs, and risperidone was significantly worse than several other SGAs.” (opens the source at this quote in a new tab)

CATIE: all-cause discontinuation over 18 months by assigned agent

“A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months.” (opens the source at this quote in a new tab)
“Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone.” (opens the source at this quote in a new tab)
“Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.” (opens the source at this quote in a new tab)

Class labeling: boxed warning and metabolic warning in the olanzapine label

“Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.” (opens the source at this quote in a new tab)
“Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain.” (opens the source at this quote in a new tab)