Antipsychotic medications form the cornerstone of schizophrenia treatment. They help reduce hallucinations, delusions, disorganized thinking, and agitation—allowing many individuals to regain stability and social functioning. But like all powerful treatments, they come with potential side effects that require careful monitoring.

This guide explains the different types of antipsychotics, how they work, and how to manage their most common and serious side effects.

1. How Antipsychotics Work

Schizophrenia involves overactivity of dopamine transmission in specific brain circuits, particularly the mesolimbic pathway. Antipsychotics primarily act by blocking dopamine D₂ receptors, helping regulate this imbalance.

However, dopamine is also important for movement, motivation, and pleasure—so blocking it in other pathways explains many side effects.

Pathway	Therapeutic / Side Effect Outcome
Mesolimbic	↓ Hallucinations & delusions (therapeutic)
Mesocortical	May worsen negative symptoms (flat affect, apathy)
Nigrostriatal	Movement disorders (EPS, Parkinsonism)
Tuberoinfundibular	↑ Prolactin → sexual & hormonal side effects

2. Classification of Antipsychotics

a. First-Generation (Typical) Antipsychotics

Examples: Haloperidol, Chlorpromazine, Fluphenazine, Trifluoperazine

• Strong D₂ receptor blockers
• Effective for positive symptoms (delusions, hallucinations)
• More likely to cause movement-related side effects

Common Side Effects:

• Extrapyramidal symptoms (EPS):
  • Acute dystonia (muscle spasms)
  • Akathisia (restlessness)
  • Parkinsonism (tremor, rigidity, bradykinesia)
• Tardive dyskinesia: late-onset involuntary facial or limb movements
• Sedation and weight gain (especially with chlorpromazine)
• Prolactin elevation → breast tenderness, galactorrhea, menstrual irregularities

Management Tips:

• Use anticholinergic agents (trihexyphenidyl, benztropine) for EPS
• Prefer lower doses in elderly or those with Parkinson’s disease
• Switch to atypical antipsychotics if side effects persist

b. Second-Generation (Atypical) Antipsychotics

Examples: Risperidone, Olanzapine, Quetiapine, Clozapine, Aripiprazole, Lurasidone, Cariprazine

• Block both dopamine D₂ and serotonin 5-HT₂A receptors
• Treat both positive and negative symptoms
• Lower risk of movement disorders, but more metabolic issues

Common Side Effects by Drug:

Drug	Key Side Effects	Notes
Risperidone / Paliperidone	↑ Prolactin, EPS at high doses	Good for acute psychosis; monitor prolactin
Olanzapine	Weight gain, diabetes, lipid abnormalities	Avoid in obesity or metabolic syndrome
Quetiapine	Sedation, orthostatic hypotension	Useful for agitation and insomnia
Clozapine	Agranulocytosis (low WBC), seizures, weight gain, sialorrhea	For treatment-resistant schizophrenia; requires regular CBC
Aripiprazole	Akathisia, insomnia	Weight-neutral; useful in adolescents
Lurasidone	Nausea, mild akathisia	Fewer metabolic effects; take with food
Ziprasidone	QT prolongation, mild sedation	Cardiac monitoring in at-risk patients
Cariprazine / Brexpiprazole	Restlessness, insomnia	Effective for negative symptoms; partial dopamine agonists

3. Clozapine: The Gold Standard (and the Most Demanding)

Clozapine remains the most effective drug for treatment-resistant schizophrenia but requires vigilance.

Unique Benefits:

• Reduces suicide risk
• Improves both positive and negative symptoms
• May restore functioning in non-responders

Major Risks:

• Agranulocytosis: potentially fatal drop in white blood cells
• Seizures (dose-dependent)
• Severe constipation (can lead to ileus)
• Sialorrhea (drooling) and weight gain

Monitoring:

• Weekly CBC for first 6 months → fortnightly → monthly thereafter
• Watch for infection signs (fever, sore throat)

4. Long-Acting Injectable (Depot) Antipsychotics

Examples: Risperidone LAI, Paliperidone Palmitate, Aripiprazole LAI, Fluphenazine Decanoate

These are administered every 2–12 weeks and improve adherence for patients who struggle with daily pills.

Advantages:

• Steady drug levels (less relapse)
• Reduced hospitalization risk
• Helpful for patients with poor insight

Possible Issues:

• Injection site pain
• Overlap dosing initially
• Same side effects as oral forms, though often milder

5. Common Non-Neurological Side Effects Across Classes

System	Side Effects	Management
Metabolic	Weight gain, hyperglycemia, dyslipidemia	Monitor BMI, glucose, lipids; promote diet & exercise; consider metformin
Cardiac	QT prolongation, orthostatic hypotension	ECG monitoring; avoid combination with other QT-prolonging drugs
Endocrine	Hyperprolactinemia → menstrual issues, sexual dysfunction	Switch to aripiprazole or quetiapine
Neurological	Akathisia, Parkinsonism, tardive dyskinesia	Use propranolol, benzodiazepines, or switch class
Gastrointestinal	Constipation (esp. with clozapine, olanzapine)	Fiber, fluids, laxatives if needed
Hematological	Agranulocytosis (clozapine)	Regular CBC monitoring

6. Monitoring Guidelines

• Baseline: weight, waist circumference, BP, fasting glucose, lipids, CBC, ECG (if needed)
• 1–3 months: recheck weight and side effects
• 6 months onward: metabolic screening and mental status review
• Encourage psychoeducation—patients who understand their medications adhere better and recognize side effects earlier.

7. When to Call the Doctor Immediately

• Sudden muscle rigidity, high fever, confusion → possible Neuroleptic Malignant Syndrome (NMS)
• New tremors, involuntary mouth or limb movements → Tardive Dyskinesia
• Severe constipation or abdominal distension (clozapine)
• Fever or sore throat (possible agranulocytosis)

8. The Takeaway

Antipsychotics remain one of modern psychiatry’s greatest achievements—restoring clarity and independence to millions. Yet, their safe use depends on precision, patience, and partnership between doctor and patient.

With the right choice, dose, and monitoring, it’s entirely possible to stay mentally well and physically healthy.

Author:
Dr. Srinivas Rajkumar T, MD (AIIMS Delhi), DNB, MBA (BITS Pilani)
Consultant Psychiatrist, Mind & Memory Clinic
Apollo Clinic Velachery (opposite Phoenix MarketCity), Chennai
📞 +91 85951 55808 | 🌐 srinivasaiims.com