Antipsychotics, also known as neuroleptics or major tranquilizers, are a class of psychotropic medications primarily available on prescription to treat psychosis. They are used in the treatment of mental disorders characterized by a disturbance of reality and perception, impaired cognitive functioning, and diminished mood.

• Primary Indication: Management of psychosis, principally Schizophrenia and schizoaffective disorders.
• Bipolar Disorder: Used together with mood stabilizers to manage manic states with psychotic symptoms.
• Other Uses: Management of psychosis associated with severe depression (psychotic depression), Alzheimer’s disease/dementia-related behavioral disturbances (use with caution), delirium, and alcohol withdrawal syndrome.

The term psychosis refers to a variety of mental disorders characterized by a loss of touch with reality. Symptoms generally include one or more of the following:

• Diminished and distorted capacity to process information and draw logical conclusions.
• Hallucinations: Usually auditory (hearing voices) or visual, but sometimes tactile or olfactory.
• Delusions: Fixed, false, and irrational beliefs.
• Incoherence or marked loosening of associations (disorganized thinking).
• Catatonic or disorganized, unpredictable behavior.
• Aggression or violence.

Antipsychotic drugs lessen these symptoms regardless of the underlying cause.

• Genetic factors: Family history of psychotic disorders.
• Substance Abuse: Alcoholism, CNS stimulants (Cocaine, Amphetamines, Khat, cathinone, methcathinone, Phencyclidine/PCP).
• Neurological Conditions: Brain tumors, brain injuries, Alzheimer's.
• Psychosis-Producing Drugs (Iatrogenic): Levodopa (used in Parkinson's, increases dopamine), Apomorphine.

Schizophrenia is a chronic, severe mental psychotic disorder characterized by disordered thinking and a profound loss of touch with reality. It involves changes in personality, inability to relate to others, disturbed mood, and impaired interpretation of the environment. Onset typically occurs during adolescence and early adulthood.

Clinical Phenotype: The presentation varies greatly depending on the balance between negative and positive symptoms.

Psychotic disorders involve imbalances in brain neurotransmitters:

• Excitatory: Dopamine, Adrenaline, Noradrenaline, Serotonin (5-HT).
• Inhibitory: Gamma-Aminobutyric Acid (GABA).

Schizophrenia is thought to be caused largely by an excessive release or dysregulation of dopamine, leading to overstimulation of brain cells. Dopamine (DA) plays critical roles in the initiation of movement, reinforcement/reward, cognitive function, regulation of prolactin release, vomiting (CTZ trigger), temperature regulation, and appetite reduction.

• Dopamine (D2) Receptor Blockade: The primary mechanism is blocking D2 receptors in the mesolimbic and mesofrontal systems. They must achieve roughly 60-80% occupancy of striatal D2 receptors for clinical efficacy.
• Serotonin (5-HT2A) Receptor Blockade: Especially prominent in Atypical (2nd generation) antipsychotics. This allows some regulatory release of dopamine in certain tracts, reducing EPS and helping treat negative symptoms.
• Collateral Receptor Blockade (Causes Side Effects):
  • Muscarinic (Cholinergic) receptors: Causes dry mouth, blurred vision, constipation, urinary retention.
  • Histamine (H1) receptors: Causes sedation and weight gain.
  • Alpha-1 Adrenergic receptors: Causes orthostatic (postural) hypotension and dizziness.

• Absorption: Readily but incompletely absorbed orally. Bioavailability is 25-65% due to significant first-pass metabolism in the liver.
• Distribution: Highly lipid-soluble and highly protein-bound (92-98%). They have a large volume of distribution (>7 L/Kg).
• Metabolism: Extensively metabolized in the liver (Cytochrome P450 system). Most have active metabolites (e.g., thioridazine is metabolized to mesoridazine, which is more potent).
• Excretion / Elimination: Eliminated mainly through the kidneys. Slow elimination with a half-life of 10-24 hours. Because they are highly lipophilic, clinical effects and metabolites can persist for weeks after discontinuation, meaning relapse may be delayed.

Also known as conventional or traditional agents. Discovered in the 1950s. They primarily improve positive symptoms of schizophrenia by competitively blocking D2 receptors. In Uganda, these are the most commonly used drugs because they are inexpensive and widely available.

Drawbacks: High risk of Extrapyramidal Side Effects (EPS). Low-potency typicals have less D2 affinity but bind strongly to non-dopaminergic receptors, causing severe sedation, hypotension, and anticholinergic effects.

• Profile:
  • The prototype first-generation (typical) antipsychotic; a low-potency phenothiazine.
  • Characterized by high sedating properties (H1 blockade), high anticholinergic effects (M1 blockade), and high hypotensive properties (Alpha-1 blockade).
  • Because it binds less tightly to D2 receptors than high-potency drugs, it has a lower risk of Extrapyramidal Side Effects (EPS), but a much higher risk of metabolic and autonomic interference.
• Indications:
  • Acute and chronic Schizophrenia; particularly useful when sedation is required for behavioral control.
  • Acute Mania in Bipolar Disorder and severe agitation in elderly patients with dementia (though used with extreme caution).
  • Alcohol-related withdrawal symptoms and psychotic behaviors.
  • Management of nausea/vomiting and intractable hiccups that do not respond to other treatments.
  • Controlling spasms in tetanus (adjunctive treatment) and induction of "artificial hibernation" in historical surgical contexts.
• Contraindications:
  • Liver disease (cirrhosis) due to extensive hepatic metabolism; bone marrow depression (risk of agranulocytosis).
  • Closed-angle glaucoma and prostatic hypertrophy (due to anticholinergic effects).
  • Note: It significantly lowers the seizure threshold; clinicians must monitor with a "fit chart" in patients with epilepsy or alcohol withdrawal.
• Dosage:
  • Oral: 100mg - 1500mg daily in divided doses (DDD); dose is highly individualized based on the severity of psychosis.
  • Injectable (IM): 25 - 200mg IM stat. Deep IM injection is required to avoid tissue irritation; can be used for continuous narcosis until the patient is calm.
  • Rectal: 100mg suppositories (OD, BD, or TDS); particularly useful for pediatric patients (>5 years) or those with severe vomiting who cannot swallow.
  • Syrups: 25mg/5mls or 100mg/5mls (Suspension); liquid forms allow for more precise titration and are harder for patients to "cheek" (hide in the mouth).

• Profile:
  • High-potency phenothiazines with a high affinity for D2 receptors in the mesolimbic and nigrostriatal pathways.
  • They carry a high EPS risk (dystonias, akathisia, parkinsonism) but have lower sedating, hypotensive, and anticholinergic effects compared to chlorpromazine.
  • Known for strong anti-hallucinogenic and anti-delusional properties.
• Indications:
  • Schizophrenia: Particularly effective for "withdrawn" patients as they are less sedating and may help with apathy.
  • Mania and Organic brain syndromes (delirium/dementia with psychosis).
  • Severe, non-psychotic anxiety that has not responded to other agents.
  • Preferred in epileptic patients compared to chlorpromazine because they have a lesser effect on the seizure threshold.
• Dosage (Trifluoperazine):
  • Oral: 5-45mg daily; often started at 2-5mg twice daily.
  • Injectable: 1-3mg deep IM (max 6mg in 24 hours) for rapid control of symptoms.

• Profile:
  • Moderate sedating effects with uniquely low EPS risk for a typical antipsychotic, because its strong internal anticholinergic activity "balances" the dopamine blockade.
  • Extremely high anticholinergic effects and significant Alpha-1 blockade.
  • Warning: Associated with dose-related retinal pigmentation (retinitis pigmentosa) and dangerous cardiac arrhythmias (QT prolongation).
• Indications:
  • Schizophrenia and Mania, primarily when other drugs cause intolerable EPS.
  • Severe agitation and behavioral problems in the elderly or in children with developmental disorders.
• Dosage:
  • 100-1000mg DDD; doses above 800mg/day are strictly avoided to prevent permanent blindness from retinal toxicity.
  • Children: 1mg/kg body weight. Must monitor BP and ECG regularly.

• Profile:
  • The most widely used high-potency typical antipsychotic.
  • Very high EPS risk; acute dystonic reactions are common, especially in young males.
  • Low sedating, low anticholinergic, and low hypotensive effects, making it "cardio-safe" in standard doses compared to phenothiazines.
• Indications:
  • Drug of choice for acute Mania and severe psychomotor agitation ("chemical restraint").
  • Schizophrenia (positive symptoms), alcohol-induced psychosis, and Delirium.
  • Intractable hiccups and Tourette’s syndrome (to reduce tics).
  • Preferred over chlorpromazine in pediatric patients (>5yrs) for severe behavioral issues and aggression.
• Dosage:
  • Oral: 5-30mg DDD (max 60mg in extreme cases).
  • Injectable: 5-20mg IM stat; can be repeated every 2-8 hours until behavioral control is achieved.
  • Pediatric: 25-50 micrograms per kg, carefully titrated.

• Trifluperidol:
  • Extremely potent; used primarily for resistant schizophrenia.
  • Dose: 0.5mg - 8mg daily in divided doses.
• Benperidol:
  • The most potent neuroleptic available in many regions; notably effective for controlling deviant sexual behaviors and antisocial personality impulsivity.
  • Dose: 0.25-1.5mg OD/BD/TDS.

This class is structurally related to phenothiazines but contains a carbon atom instead of a nitrogen atom in the central ring. Their usage has decreased with the advent of atypicals.

• Flupentixol (Depixol, Fluanxol):
  • Unique among typicals for having "activating" or mild mood-elevating properties at low doses.
  • Excellent for patients with "negative" features of schizophrenia (apathy, social withdrawal).
  • Dose: 3-9mg (max 18mg daily).
• Zuclopenthixol (Clopixol, Acuphase):
  • Acuphase is specifically used for the short-term (2-3 day) management of acute psychosis or mania; it has a rapid onset and sustained effect.
• Nursing Note: NEVER give these neuroleptic injectables via the IV route. This can cause immediate cardiovascular collapse, severe laryngospasm, and fatal postural hypotension.

These are esterified antipsychotics dissolved in vegetable oils (like sesame or coconut oil). They are injected deep IM to create a reservoir that is slowly released over weeks.

• Indications:
  • Maintenance therapy for chronic schizophrenia to prevent relapse.
  • Ensures 100% medication compliance in patients who lack insight or tend to stop oral medications.
• Haloperidol decanoate: 50mg to 150mg IM every 4 weeks. High risk of EPS; often co-prescribed with anticholinergics.
• Fluphenazine decanoate (Modecate): Extremely potent. Requires a 12.5mg test dose to check for severe reactions; maintenance is 25-50mg every 2-4 weeks.
• Flupentixol decanoate (Depixol): Initially 20mg IM, then 40mg every 2-4 weeks. The preferred depot for patients with depressive or negative symptoms.
• Fluspirilene (Redeptin): Aqueous-based rather than oil-based; 2-4mg IM given weekly.

Introduced in the 1990s. They act as Serotonin-Dopamine Antagonists (SDAs), blocking 5-HT2A receptors strongly and D2 receptors to a lesser degree. They are superior because they treat BOTH positive and negative symptoms of schizophrenia and carry a much lower risk of Extrapyramidal Side Effects (EPS). However, they are highly associated with Metabolic Syndrome (rapid weight gain, diabetes mellitus, hypercholesterolemia).

• Formulations:
  • Available in standard oral tablets, M-Tabs (rapidly dissolving/orally disintegrating tablets to prevent "cheeking"), and a long-acting injectable (Risperdal Consta) given every 2 weeks.
• Pharmacology:
  • A potent D2 and 5-HT2A antagonist. At lower doses, it effectively treats psychosis with minimal motor side effects.
  • At doses > 6 mg, its binding profile shifts; it saturates D2 receptors to such an extent that it functions more like a typical antipsychotic, causing significantly increased EPS risk.
• Unique Side Effect:
  • The most likely atypical to induce severe hyperprolactinemia. It lacks the blood-brain barrier selectivity of other atypicals, leading to high dopamine blockade in the pituitary gland.
  • Manifests clinically as gynecomastia (breast tissue in males), galactorrhea (milky nipple discharge), amenorrhea (loss of periods), and long-term risks of osteoporosis.
• Other Effects:
  • Causes dose-dependent weight gain, sedation, orthostatic hypotension (via alpha-1 blockade), and chronic fatigue.

• Dosing:
  • Dose: 5mg - 20mg/day, typically given as a single daily dose (OD) at night (nocte) to manage its heavy sedating effects.
• Metabolic Profile:
  • Highest risk among second-generation antipsychotics for severe weight gain and metabolic syndrome.
  • Patients can gain significant weight (often 10-20+ lbs) rapidly. It causes profound insulin resistance and hyperlipidemia, leading to a high risk of New-Onset Diabetes Mellitus.
• Side Effects:
  • Causes heavy sedation and daytime somnolence; transient hypotension and dizziness upon standing.
  • Anticholinergic effects such as dry mouth and constipation.
  • May cause elevated liver enzymes (LFTs), requiring baseline and periodic blood monitoring.

• Dosing & Utility:
  • Dose: 100 - 750mg DDD. Extremely versatile; low doses (25-50mg) are used for sleep, moderate doses for bipolar depression, and high doses for schizophrenia.
• Side Effects:
  • Extremely sedating due to very high H1 receptor affinity; often used off-label as a sleep aid.
  • Most likely atypical to cause significant orthostatic hypotension because of its potent alpha-1 adrenergic antagonism.
  • Causes moderate weight gain and can increase blood sugar/cholesterol levels.
• EPS Profile:
  • Very low EPS risk because it "hits and runs" the D2 receptor (rapid dissociation), making it a preferred choice for patients with Parkinson’s disease who develop psychosis.

• Clinical Status:
  • Dose: 100 - 900mg DDD. Historically the first atypical; remains the "gold standard" and is highly effective for treatment-resistant schizophrenia (failure of 2 or more other trials).
  • Proven to significantly reduce suicidal behavior in schizophrenic patients.
• Severe Side Effects:
  • Agranulocytosis: A potentially fatal drop in white blood cells (specifically the Absolute Neutrophil Count/ANC). Occurs in ~1-2% of patients. Nurses must immediately report sore throat, fever, or malaise as these are early signs of infection.
  • Mandatory Monitoring: Requires a strict national registry and frequent blood draws (weekly for the first 6 months, then bi-weekly, then monthly) to dispense the drug.
  • Seizures: Significantly reduces the seizure threshold in a dose-dependent manner (affects 1-5% of patients). May require co-administration of anticonvulsants like Valproate.
  • Gastrointestinal Hypomotility: Severe constipation that can progress to fatal paralytic ileus or bowel obstruction.
  • Others: Extreme hypersalivation (wet pillow syndrome), massive weight gain, myocarditis (inflammation of the heart muscle), and profound sedation.

Caused by D2 blockade in the nigrostriatal pathway. These are movement disorders that are far more common with typical, high-potency drugs (like Haloperidol) than with atypicals.

1. Acute Dystonia:
   • Symptoms: Uncontrolled, painful muscular spasms. Includes Oculogyric crisis (eyes fixed upward), Torticollis (neck twisted to side), and Opisthotonus (arching of the back). Can cause laryngeal dystonia, which is a life-threatening airway obstruction.
   • Management: Medical emergency. Administer anticholinergics like Benzhexol (Artane) or Benztropine (Cogentin) IM/IV stat for immediate relief.
2. Pseudo-Parkinsonism:
   • Symptoms: Mimics Parkinson’s disease. Includes "pill-rolling" tremors, cogwheel rigidity, bradykinesia (poverty of movement), and a mask-like facial expression.
   • Management: Decrease the dose of the antipsychotic or switch to a drug with lower D2 affinity. Oral anticholinergics (Artane) are standard treatment.
3. Akathisia:
   • Symptoms: Motor restlessness—patients describe "crawling out of their skin." Includes constant pacing, shifting weight, and inability to remain still. It is a major risk factor for suicide due to the intense distress.
   • Management: Propranolol (Beta-blocker) is the first-line treatment. Benzodiazepines may also help. Crucial: Do not confuse this with worsening psychosis and increase the neuroleptic dose!
4. Tardive Dyskinesia (TD):
   • Symptoms: Involuntary, repetitive movements resulting from long-term D2 supersensitivity. Includes lip-smacking, tongue thrusting, and choreic movements of the limbs.
   • Management: Often permanent if not caught early. Perform regular AIMS (Abnormal Involuntary Movement Scale) exams. If detected, switch to Clozapine, which has the lowest risk of worsening TD.

• Description: A rare, idiosyncratic, medical emergency caused by massive dopamine depletion. It carries a high mortality rate and requires immediate recognition by nursing staff.
• Classic Tetrad of Symptoms:
  • Hyperpyrexia: High fever (often >38.5°C or 101°F) accompanied by diaphoresis (sweating).
  • Muscle Rigidity: "Lead-pipe" stiffness; the muscles are so tight they begin to break down (rhabdomyolysis).
  • Autonomic Instability: Unstable heart rate, fluctuating BP, and rapid breathing.
  • Altered Consciousness: Confusion, agitation, or progressing to a coma.
• Nursing & Medical Management:
  • Stop all antipsychotics immediately. Transfer to an ICU or acute medical ward.
  • Aggressive cooling (ice packs, cooling blankets) and IV fluids to prevent kidney failure from muscle breakdown.
  • Administer Dantrolene (muscle relaxant) and Bromocriptine (dopamine agonist) as ordered.

• Assessment: Differentiate between akathisia (motor restlessness) and psychotic agitation. Inform the physician, as increasing the antipsychotic dose for akathisia will severely worsen the condition.
• Monitoring: Observe the patient regularly for abnormal movements using standardized scales (e.g., AIMS - Abnormal Involuntary Movement Scale) to catch Tardive Dyskinesia early.
• Safety: Take all seizure precautions. Institute fall precautions due to orthostatic hypotension.
• Administration: Do not mix liquid concentrates arbitrarily; dilute with approved liquids (e.g., fruit juice) to mask the taste and reduce GI irritation. Avoid skin contact with concentrates.

• Adherence: Teach the importance of absolute drug compliance. Do NOT discontinue medications immediately after feeling well, as relapse is highly likely. Do not stop long-term use abruptly to avoid withdrawal dyskinesias.
• Safety: Be cautious while driving or operating dangerous machinery due to sedation.
• Lifestyle: Stop alcohol consumption completely, as it exacerbates CNS depression. Do not consume other OTC medications without physician approval. Consult physician regarding smoking (smoking induces liver enzymes and can lower drug levels, notably Clozapine and Olanzapine).
• Thermoregulation: Dress warmly in cold weather and avoid extended exposure to extreme heat. Body temperature regulation (hypothalamus) is impaired by these medications.
• Danger Signs to Report: Immediately report sore throat, severe headache, rapid heart rate, difficulty urinating, muscle twitching/tremors, dark urine, yellow skin/eyes (jaundice), skin rash, or seizures.
• Identification: Carry an identification card at all times listing the prescribed medication being taken.

• Patil, M. C. (n.d.). Antipsychotic Drugs [PDF Presentation]. KAHER IONS, Belagavi.
• Stahl, S. M. (2013). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed.). Cambridge University Press.
• American Psychiatric Association. (2020). Practice Guideline for the Treatment of Patients With Schizophrenia (3rd ed.).
• U.S. Food and Drug Administration (FDA). (2008). FDA Requests Boxed Warnings on Older Class of Antipsychotic Drugs.
• Uganda Clinical Guidelines (UCG) for Psychiatric Management and Typical Antipsychotic Utilization.