This topic includes both first and second generation antipsychotics.

Antipsychotics are effective for the symptoms of schizophrenia. Positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, and motivation. Antipsychotics can also cause side effects. These include extrapyramidal symptoms such as dyskinesias (repetitive, involuntary, and purposeless body or facial movements), Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation), and dystonias (muscle contractions causing unusual twisting of parts of the body, most often in the neck). These effects are caused by the dopamine receptor antagonist action of antipsychotics. Other side effects may include weight, hormonal and metabolic changes, increased sedation, and ventricular anomalies (QTc prolongation).

What is the evidence for any antipsychotic efficacy compared to placebo?

Overall, moderate to high quality evidence finds a medium-sized effect of greater total symptom improvement with antipsychotics than with placebo. There was less variability in the response to antipsychotics than in the response to placebo, with older studies, those with younger patients, higher dose treatments, and greater mean difference in symptom change being associated with the least variability in response.

For particular antipsychotics, there were symptom improvements with (in descending order of efficacy compared to placebo): clozapine, amisulpride, thiotixene, zotepine, olanzapine, perphenazine, risperidone, thioridazine, zuclopenthixol, paliperidone, sulpiride, haloperidol, loxapine, chlorpromazine, flupentixol, clopenthixol, molindone, quetiapine, aripiprazole, ziprasidone, sertindole, asenapine, lurasidone, cariprazine, iloperidone, and brexpiprazole. There were no significant differences in symptoms between placebo and penfluridol, pimozide, perazine, fluphenazine, trifluoperazine, and levomepromazine.

For social functioning, there were improvements with (in descending order of efficacy compared to placebo) thioridazine, olanzapine, paliperidone, quetiapine, lurasidone, and brexpiprazole. There were no improvements in social functioning between placebo and aripiprazole, sertindole, amisulpride, ziprasidone, flupentixol, or risperidone.

For all-cause discontinuation (in descending order of effects, first being best), there was less discontinuation with clopenthixol, amisulpride, olanzapine, paliperidone, thiotixene, thioridazine, clozapine, loxapine, iloperidone, perphenazine, aripiprazole, risperidone, zuclopenthixol, zotepine, asenapine, quetiapine, lurasidone, brexpiprazole, haloperidol, and ziprasidone. There were no differences between placebo and perazine, levomepromazine, flupentixol, molindone, fluphenazine, chlorpromazine, cariprazine, sulpiride, sertindole, penfluridol, trifluoperazine, and pimozide.

For side effects (in ascending order of harm compared to placebo), there was less use of antiparkinson drugs with clozapine than with placebo, and more use of antiparkinson drugs with paliperidone, ziprasidone, risperidone, lurasidone, zotepine, cariprazine, chlorpromazine, sulpiride, perphenazine, molindone, zuclopenthixol, trifluoperazine, flupentixol, haloperidol, loxapine, penfluridol, fluphenazine, chlorpromazine, thiotixene, and pimozide.

There was more akathisia with aripiprazole, ziprasidone, thioridazine, asenapine, amisulpride, chlorpromazine, thiotixene, risperidone, cariprazine, loxapine, haloperidol, lurasidone, trifluoperazine, sulpiride, molindone, penfluridol, pimozide, fluphenazine, flupentixol, and zuclopenthixol.

There was more weight gain with haloperidol, amisulpride, asenapine, risperidone, paliperidone, clozapine, quetiapine, iloperidone, chlorpromazine, sertindole, olanzapine, and zotepine.

There was less prolactin elevation with aripiprazole, clozapine, and zotepine, and more prolactin elevation with olanzapine, asenapine, lurasidone, sertindole, haloperidol, amisulpride, risperidone, and paliperidone.

There was more sedation with aripiprazole, lurasidone, haloperidol, risperidone, asenapine, loxapine, olanzapine, chlorpromazine, thioridazine, thiotixene, ziprasidone, perazine, clozapine, clopenthixol, quetiapine, sulpiride, zotepine, and zuclopenthixol.

There was more QTc prolongation with quetiapine, olanzapine, risperidone, iloperidone, ziprasidone, amisulpride, and sertindole.

There was more anticholinergic side-effects haloperidol, olanzapine, clozapine, chlorpromazine, zotepine, iloperidone, thioridazine, and quetiapine.

October 2020

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as amisulpride are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions).

Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for amisulpride?

High quality evidence suggests amisulpride may retain more patients in treatment, and be more effective for global state and negative symptoms than placebo. Moderate quality evidence suggests amisulpride may cause more extrapyramidal symptoms than placebo.

High quality evidence suggests amisulpride may retain more patients in treatment, and be more effective for global state, mental state and negative symptoms, but not positive symptoms, than first generation antipsychotics. Amisulpride may be less likely to cause at least one adverse event or extrapyramidal symptom when compared to first generation antipsychotics.

Moderate quality evidence suggests no differences in any outcome compared to other second generation antipsychotics in general. Moderate to low quality evidence suggests fewer people leaving the study early due to inefficacy with amisulpride compared to ziprasidone. Moderate to high quality evidence suggests amisulpride is associated with less weight gain than risperidone or olanzapine. Moderate quality evidence suggests agitation may be reported more often by patients receiving amisulpride than other second generation antipsychotics, with no difference in cardiac effects or extrapyramidal symptoms between amisulpride and risperidone, olanzapine or ziprasidone.

October 2020

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as aripiprazole are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions).

Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for aripiprazole?

High quality evidence suggests aripiprazole reduces psychotic relapse and increases compliance with study protocols when compared to placebo. Moderate quality evidence suggests aripiprazole may also increase study retention rates. Moderate to low quality evidence suggests no differences in any adverse effect apart from possible reduced prolactin levels with aripiprazole.

High quality evidence from the most recent review suggests aripiprazole should retain more patients in treatment than first generation antipsychotics. Moderate quality evidence suggests no differences in global state, mental state or quality of life between aripiprazole and first generation antipsychotics. Aripiprazole may be associated with a lower risk of akathisia and other extrapyramidal symptoms, hyperprolactinaemia, blurred vision, sinus tachycardia, dizziness and nausea, than first generation antipsychotics.

Moderate to high quality evidence suggests no differences in global state or leaving the study early between aripiprazole and olanzapine or risperidone, although aripiprazole may be less effective than olanzapine for mental state. Compared to olanzapine or risperidone, aripiprazole may be associated with less cholesterol and less prolactin increases, with no differences in extrapyramidal side effects or glucose levels. Compared to olanzapine, aripiprazole may be associated with less weight gain and less sedation. When compared to risperidone, patients on aripiprazole reported less cardiac side effects, but a higher incidence of tremor. There were no differences in weight gain between risperidone and aripiprazole.

October 2020

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as asenapine are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia, although the evidence for this is weak. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as blonanserin are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for blonanserin?

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as brexpiprazole are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extrapyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for brexpiprazole?

Moderate to high quality evidence suggests brexpiprazole is more effective for symptoms than placebo, with no differences between 2mg/day and 4mg/day dose. However, there was a higher risk of weight gain with brexpiprazole, and 4mg/day resulted in more extrapyramidal symptoms than 2mg/day.

October 2020

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as cariprazine are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia, although the evidence for this is weak. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for cariprazine?

Moderate to high quality evidence finds greater improvement in symptoms and quality of life with low (<6mg/day) or high dose (>6mg/day) cariprazine compared to placebo. However, there were more treatment emergent adverse effects with cariprazine, particularly akathisia and parkinsonian.

October 2020

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as carpipramine are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia, although the evidence for this is weak. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias (muscle contractions causing unusual twisting of parts of the body, most often in the neck). These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for carpipramine?

Moderate quality evidence suggests no differences in discontinuation, response rates, or side effects between carpipramine and first generation antipsychotics clofluperol, oxypertine, penfluridol, or pimozide.

October 2020

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as clocapramine are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia, although the evidence for this is weak. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for clocapramine?

Moderate quality evidence suggests no differences between clocapramine and first or second generation antipsychotics for discontinuation or response, although in comparison with second generation antipsychotics only, clocapramine may be less effective. There was less incidence of headaches and decreased appetite with clocapramine.

October 2020

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Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as clotiapine are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia, although the evidence for this is weak. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extrapyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for clotiapine?

Moderate to low quality evidence finds no differences in global state or hospital discharge rates between clotiapine and first generation antipsychotics (chlorpromazine, perphenazine, trifluoperazine or zuclopenthixol acetate). Lower quality evidence suggests clotiapine may induce fewer parkinsonian symptoms than first generation antipsychotics. Low quality evidence is unable to determine any benefit or harm of chlorpromazine or benzodiazapines over clotiapine.

October 2020

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