List of Atypical Antipsychotics
The current list of atypical antipsychotics includes clozapine, risperidone, olanzapine, quetiapine, asenapine, aripiprazole, ziprasidone, lurasidone, iloperidone, paliperidone, and sertindole. 1, 2
Mechanism of Action
Atypical antipsychotics differ from typical antipsychotics primarily in their mechanism of action:
- All atypical antipsychotics have significant serotonin 5-HT2A receptor antagonism 2
- Most also have direct or indirect stimulation of 5-HT1A receptors 2
- They have relatively lower dopamine D2 receptor blockade compared to typical antipsychotics 2
- Some also act on other serotonin receptors (5-HT2C, 5-HT6, 5-HT7) 2
This contrasts with typical antipsychotics (like haloperidol), which primarily act as strong dopamine D2/D3 receptor antagonists.
Clinical Advantages of Atypical Antipsychotics
Atypical antipsychotics offer several advantages over typical antipsychotics:
- Lower risk of extrapyramidal side effects (EPS) - this is the defining characteristic of atypical antipsychotics 3
- Reduced risk of tardive dyskinesia - important as TD increases mortality rates 3
- Less prolactin elevation (with exceptions like risperidone) 2
- Potential cognitive benefits - may be superior for some domains of cognition 3
- Efficacy for negative symptoms - though this varies between agents 4
Notable Individual Agents
Clozapine
- Unique among atypicals for efficacy in treatment-resistant schizophrenia 3
- Requires regular blood monitoring due to risk of agranulocytosis 1
- FDA-indicated for reducing suicidal behavior in schizophrenia 5
Risperidone
- Higher risk of EPS compared to other atypicals 1
- More likely to cause prolactin elevation 2
- Typical dosage range: 1.25-3.5 mg/day 6
Asenapine
- Administered as sublingual tablets that dissolve under the tongue 7
- Eating and drinking should be avoided for 10 minutes after administration 7
- FDA-indicated for bipolar I disorder as adjunctive treatment 7
Side Effect Considerations
Despite their advantages, atypical antipsychotics have important side effects to monitor:
- Weight gain - can be extreme with some agents and is the most common significant problem 1
- Metabolic changes - hyperglycemia, diabetes, dyslipidemia 8
- Orthostatic hypotension - particularly important in cardiovascular disease 1, 6
- QT prolongation - varies between agents 1, 6
- Hematological effects - agranulocytosis with clozapine, but can occur with any antipsychotic 1
- Hepatic effects - may produce elevations in hepatic transaminase levels 1
Monitoring Recommendations
When using atypical antipsychotics, appropriate monitoring includes:
- Regular assessment for abnormal movements using standardized scales 6
- Blood glucose monitoring, especially in patients with risk factors for diabetes 8
- Weight monitoring 1
- Baseline and follow-up liver function tests 1
- For clozapine: weekly blood counts during first 6 months, then biweekly 1
- For quetiapine: baseline and 6-month follow-up eye examinations 1
Atypical antipsychotics represent a significant advancement in the treatment of psychotic disorders, but careful selection based on individual patient factors and side effect profiles is essential for optimizing outcomes.