Which medications in the drug class Antipsychotics, 2nd Generation are used in the treatment of Schizophrenia?

Updated: Mar 16, 2018
  • Author: Frances R Frankenburg, MD; Chief Editor: Glen L Xiong, MD  more...
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Answer

Antipsychotics, 2nd Generation

Second-generation (novel or atypical) antipsychotics, with the exception of aripiprazole, are dopamine D2 antagonists, but are associated with lower rates of extrapyramidal adverse effects and TD than the first-generation antipsychotics. However, they have higher rates of metabolic adverse effects and weight gain.

Asenapine (Saphris)

Asenapine is indicated for acute and maintenance treatment of schizophrenia. It is absorbed poorly in the gastrointestinal (GI) tract and thus is available in a sublingual form. The most common side effects include sedation, weight gain, dizziness, extrapyramidal symptoms, and oral hypoesthesia.

Asenapine's mechanism of action is unknown. Its efficacy is thought to be mediated through a combination of antagonist activity at dopamine D2 and serotonin 5-HT2 receptors. Asenapine exhibits high affinity for serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors; dopamine D2, D3, D4, and D1 receptors; alpha1- and alpha2-adrenergic receptors; and histamine H1 receptors, with moderate affinity for H2 receptors. The addition of serotonin antagonism to dopamine antagonism may improve the negative symptoms of psychoses and may reduce the incidence of extrapyramidal adverse effects when compared with typical antipsychotics.

Asenapine transdermal (Secuado)

Asenapine transdermal is indicated for the treatment of schizophrenia. The patch is applied once daily. Adverse reactions were consistent with sublingual asenapine. 

The mechanism of action is unknown. The efficacy thought to be mediated via combined antagonist activity at dopamine D2 and serotonin type 2 (5-HT2) receptors.

Clozapine (Clozaril, FazaClo)

Clozapine is the oldest atypical antipsychotic agent and probably the most effective. Because it is associated with about a 1% risk of agranulocytosis, patients must undergo white blood cell (WBC) count monitoring every week for the first 6 months (the period of greatest risk), then every 2 weeks for 6 months, and finally every 4 weeks, as long as the absolute neutrophil count (ANC) is normal. If the ANC drops, a strict protocol of monitoring and possibly medication cessation must then be followed.

Clozapine is an antagonist at adrenergic, cholinergic, histaminergic, and serotonergic receptors. It has some dopamine D2 antagonism and high D4 affinity. It carries a high adverse effect burden, including sedation, drooling, constipation, and possible cardiac effects. Because it can cause agranulocytosis, patients must have regular blood tests. It is indicated for refractory schizophrenia and for reducing the risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder.

The anticholinergic adverse effects, sedation, and drooling can be burdensome. Constipation and cardiac adverse effects (cardiomyopathy and myocarditis) can be life-threatening. However, approximately one third of patients who have not responded to conventional antipsychotic agents do better on clozapine. Violence, hostility, and suicidality may be diminished with the use of clozapine.

Iloperidone (Fanapt)

Iloperidone is indicated for acute treatment of schizophrenia. Its precise mechanism of action is unknown, but it is known to antagonize dopamine D2 and serotonin 5-HT2 receptors. However, it shows high affinity for 5-HT2A, D2, and D3 receptors and low-to-moderate affinity for D1, D4, H1, 5-HT1A, 5HT6, 5-HT7, and NE alpha1 receptors. Adverse effects include dizziness, orthostatic hypotension, tachycardia, weight gain, dry mouth, and sedation. Iloperidone causes fewer extrapyramidal symptoms than do other antipsychotics.

Lurasidone (Latuda)

Lurasidone is an atypical antipsychotic whose precise mechanism of action is unknown. It is a dopamine D2 and serotonin 5-HT2A receptor antagonist. It is indicated for schizophrenia in adults and is approved by the FDA to treat schizophrenia in adolescents (aged 13-17 y)

A major route of metabolism for lurasidone is via CYP3A4. Dose reduction is recommended in the presence of moderate CYP3A4 inhibitors. Coadministration with strong CYP3A4 inducers is not recommended.

Olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv)

Olanzapine is a selective monoaminergic antagonist at serotonin, dopamine D1-4, muscarinic, histamine H1, and alpha1-adrenergic receptors. It is available as a regular tablet, a rapidly disintegrating tablet, a short-acting injectable solution, and a long-acting injectable formulation. The most common side effects of olanzapine include weight gain, sedation, akathisia, hypotension, dry mouth, and constipation. It is also approved by the FDA to treat schizophrenia in adolescents.

Paliperidone (Invega, Invega Sustenna, Invega Trinza)

Paliperidone is the major active metabolite of risperidone and was the first oral agent to allow once-daily dosing. It is indicated for acute and maintenance treatment of schizophrenia adults and is also approved by the FDA to treat schizophrenia in adolescents. Its mechanism of action not completely understood but is thought to involve antagonism of dopamine D2 and serotonin 5HT-2A receptors. Paliperidone also elicits antagonist activity at adrenergic alpha1 and alpha2 receptors and histamine H1 receptors. Paliperidone is available in an osmotic delivery capsule and in long-term injectable IM forms (once monthly, q3mo).

Quetiapine (Seroquel, Seroquel XR)

Quetiapine may act by antagonizing dopamine and serotonin receptors. It is used for treatment of schizophrenia in adults and is also approved by the FDA to treat schizophrenia in adolescents. Quetiapine is available in immediate-release and extended-release tablets. Major adverse effects include sedation, orthostatic hypotension, akathisia, dry mouth, and weight gain.

Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

Risperidone has both dopamine D2 and serotonin 5-HT2 antagonism. It is approved by the FDA to treat schizophrenia in adults and adolescents. It is available in tablets, oral disintegrating tablets, and an oral solution, as well as a long-acting form for IM injection that uses microspheres made of biodegradable polymers. It has few anticholinergic effects. Primary adverse effects of risperidone include mild sedation, hypotension, akathisia, increase in prolactin, and weight gain.

Ziprasidone (Geodon)

Ziprasidone antagonizes dopamine D2, serotonin 5-HT2, histamine H1, and alpha1-adrenergic receptors. It is available in capsule and short-acting IM injection forms. It is indicated for treatment of acute agitation in patients with schizophrenia. Ziprasidone appears to cause less weight gain, hyperglycemia, and hyperlipidemia than other drugs in its category do.

Cariprazine (Vraylar)

The precise mechanism by which cariprazine works for schizophrenia is unknown. Efficacy could be mediated through a combination of partial agonist activity at central dopamine (D2) and serotonin 5-HT1A receptors. Cariprazine forms 2 major metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), which have in vitro receptor binding profiles similar to the parent drug.


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