Antipsychotics How They Work Uses Dosing and Side Effects

Antipsychotics are a class of medications used to manage psychotic symptoms such as delusions, hallucinations, and disorganized thinking. They play a central role in treating several mental health conditions, most notably schizophrenia and schizoaffective disorder, but they are also used in certain bipolar disorders, major depressive disorder with psychotic features, and some forms of agitation or behavior problems. While they cannot cure these conditions, antipsychotics can reduce symptoms, prevent relapse, and help people engage more effectively in other therapies and daily life activities.

How antipsychotics work

Most traditional (first-generation) antipsychotics work primarily by blocking dopamine D2 receptors in brain circuits involved in thinking and perception. This dopaminergic blockade helps reduce positive symptoms such as hallucinations and delusions. However, blocking dopamine in other pathways can produce movement-related side effects and hormonal changes.

Many newer (second-generation or atypical) antipsychotics also affect serotonin receptors, particularly 5-HT2A receptors, in addition to blocking D2 receptors. This broader receptor activity can lower the risk of some movement problems and may offer some benefit for mood and negative symptoms, but it can also lead to metabolic effects like weight gain and changes in blood sugar and lipids. The balance of benefits and possible adverse effects varies by drug and by person.

Common uses and conditions treated

• Schizophrenia and schizoaffective disorder
• Bipolar I or II disorder with manic, hypomanic, or psychotic features
• Major depressive disorder with psychotic features (usually in combination with antidepressants)
• Acute agitation or behavioral disturbance in some settings
• Irritability associated with autism spectrum disorder (antipsychotics may be used under medical supervision)
• Some dementia-related behavioral symptoms—note: antipsychotics are used cautiously and are associated with higher mortality risk in older adults with dementia; alternatives and careful monitoring are essential

Typical dosages

Dosing varies widely by drug, by the condition being treated, and by individual factors such as age, body weight, and prior response. The following ranges are for general educational context and are not a substitute for a clinician’s prescription.

First-generation (typical) antipsychotics

• Haloperidol: commonly started around 0.5–2 mg two to three times daily; gradual adjustment as needed. General daily ranges often extend to about 5–20 mg overall, depending on response and tolerance. For acute agitation or severe symptoms, short-acting intramuscular (IM) dosing may be used under medical supervision (e.g., 2–5 mg, sometimes repeated).
• Chlorpromazine: often started at 25–100 mg daily in divided doses, then titrated based on response and tolerability.

Second-generation (atypical) antipsychotics

• Risperidone: typically 1–2 mg once daily, increasing gradually to 4–6 mg daily as needed.
• Olanzapine: often started at 5–10 mg daily, with typical effective ranges 10–20 mg daily.
• Quetiapine: for psychosis or mood episodes, common starting dose around 50 mg daily (evening), with gradual increases; higher doses (300–400 mg daily or more) are used for mood stabilization in some cases.
• Aripiprazole: commonly 10–15 mg once daily, adjustable in the 5–30 mg range depending on response and tolerability.
• Ziprasidone: often 20–40 mg twice daily with meals; typical maintenance ranges 40–80 mg twice daily.
• Lurasidone: usually 40–60 mg daily with food, sometimes increasing to 80–120 mg for certain conditions.
• Cariprazine: often 1.5 mg daily, titrating up to 3–6 mg daily based on response and tolerability.
• Clozapine: started at very small doses (e.g., 12.5 mg daily) and titrated up; typical effective ranges are often in the 300–450 mg daily range, though higher doses may be used in some cases. Clozapine requires specific blood monitoring due to risk of agranulocytosis.

Potential side effects and monitoring

Side effects vary by drug and person. Some are common across many antipsychotics, while others are more drug-specific.

• Movement-related effects (extrapyramidal symptoms or EPS): dystonia (muscle spasms), akathisia (restlessness), parkinsonism (rigidity), and, with long-term use, tardive dyskinesia (involuntary movements).
• Metabolic and weight-related effects: weight gain, increased blood sugar, and lipid changes are more common with many second-generation agents.
• Hormonal and breast-related effects: increased prolactin can cause menstrual changes, galactorrhea, or sexual side effects.
• Sedation and cognitive slowing: some antipsychotics may cause drowsiness or slowed thinking, especially when first starting or at higher doses.
• Anticholinergic effects: dry mouth, constipation, urinary retention, especially with some agents.
• Cardiac effects: some drugs can prolong the QT interval, which may raise the risk of abnormal heart rhythms in people with certain heart conditions or who take other QT-prolonging drugs.
• Rare but serious: neuroleptic malignant syndrome (NMS) is a medical emergency characterized by high fever, muscle rigidity, and altered mental status.
• Clopazine-specific monitoring: agranulocytosis (a dangerous drop in white blood cells) and severe infections require regular blood tests and close clinical monitoring.

Monitoring is essential. Typical monitoring plans include:

• Baseline assessments: weight, height, waist circumference, blood pressure, fasting glucose or HbA1c, fasting lipid panel, liver and kidney function tests, EKG if indicated, and history of heart disease or seizures.
• Ongoing metabolic monitoring: weight and waist circumference regularly; fasting glucose/HbA1c and lipids every 3–12 months depending on risk and the drug used.
• Movement monitoring: check for EPS and tardive dyskinesia at regular visits; use standardized scales if available.
• Avoiding drug interactions: review all medications, including over-the-counter and herbal supplements, for potential interactions.

Interactions with other medications

Antipsychotics can interact with other medicines and substances in ways that affect safety and effectiveness. Key points include:

• Central nervous system depressants (for example, alcohol, benzodiazepines) can amplify sedation and coordination problems.
• Other drugs that affect heart rhythm can increase the risk of QT prolongation when taken with certain antipsychotics.
• Anticholinergic medicines can intensify anticholinergic side effects (dry mouth, constipation) with some antipsychotics.
• Dopamine-related meds used for Parkinson’s disease can lessen the antipsychotic effect; adjustments may be needed under clinician supervision.
• Some antipsychotics are processed by liver enzymes (such as CYP450 families); smoking, certain foods, or other medications can speed up or slow down drug clearance, altering levels in the blood.
• Clzoapine has notable drug interactions and requires strict blood monitoring due to the risk of serious infections and blood cell suppression.

Important considerations for patients

• Adherence and consistency are important. Take doses as prescribed, and do not stop abruptly without medical guidance, as withdrawal or relapse can occur.
• Pregnancy and lactation: discuss plan with a clinician. Some antipsychotics are used during pregnancy when benefits outweigh risks, but there can be effects on the fetus.
• Driving and activities that require alertness: some antipsychotics can cause sedation or drowsiness, especially when starting treatment or changing doses.
• Diet and exercise: be aware of metabolic side effects; engage in healthy eating and regular physical activity as advised by your health care team.
• Family and caregiver support: inform trusted people about signs of serious side effects (such as extreme confusion, fever, muscle rigidity, severe sleepiness, or signs of infection) that warrant urgent care.
• Dementia considerations: use with caution in older adults with dementia-related psychosis due to higher mortality risk; alternative approaches should be considered and discussed with a clinician.

Putting it into practice: practical tips for discussions with your clinician

• Prepare a symptom diary: note when psychotic symptoms improve and what side effects you notice, along with any changes in mood, energy, or weight.
• Ask about monitoring: which tests and checks are planned, how often, and what the results mean for your treatment plan.
• Discuss plans if side effects occur: dose adjustments, switching to a different antipsychotic, or adding supportive therapies such as counseling or sleep management.
• Clarify dosing if you have trouble taking pills: some medications have long-acting forms or alternative dosing schedules; your clinician can explain options.
• Talk about interactions: share all medicines you take, including supplements and over-the-counter products, to minimize adverse interactions.

If you have questions about a specific antipsychotic, its intended use, or how to monitor for side effects, talk with a clinician who can tailor information to your health history and current medications. Seek urgent care if you experience severe side effects such as high fever with muscle stiffness, confusion, fainting, chest pain, or significant breathing problems.