Antipsychotic Side Effects

Group of potentially serious adverse effects associated with antipsychotic medications or metoclopramide
Antagonize D2 receptors in nigrostriatal pathway
Movement related side effects

Repetitive, involuntary, purposeless body or facial movements
Ex: Lip smacking, tongue movements, finger movements

Occurs after longer duration of use, may be permanent

VMAT2 inhibitors
Valbenazine, deutetrabenazine preferred over tetrabenazine

Clonazepam
Gingko biloba

Amantadine
Deep brain stimulation

VMAT2: Vesicular monoamine transporter 2

Medications reversibly inhibit VMAT2 transporter which results in:
Decreased uptake of monoamines into synaptic vesicles
Depletion of monoamine (dopamine) stores
Overall: Less dopamine available at the substantia nigra (supersensitive D2 receptors)

Tardive dyskinesia

not recommended

40mg daily

Chorea-Huntington’s Disease

none

Tardive dyskinesia, Chorea-Huntington’s Disease

none

increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington disease. Warning based off treatment with Tetrabenazine but applied to both medications.

Extreme form of internal or external restlessness, inability to sit still, urge to move constantly
Onset: 2-3 weeks of treatment

Higher doses of antipsychotics
Low serum iron
Females

Decrease dose or switch antipsychotics
Propranolol 30-120 mg daily (divided)
Benztropine 2-4 mg daily

Muscle tension disorder, strong muscle contractions, unusual twisting of parts of body especially neck
Onset: 24-96 hours

High potency FGAs > low potency FGAs
Risperidone, paliperidone
Younger age
Males
Large muscle mass
Early in course of patient’s antipsychotic treatment

Anticholinergics:
Diphenhydramine 25-50 mg IM
Benztropine 1-2 mg IM

Discontinue or reduce dose of antipsychotic if possible

IM anticholinergic is necessary if administering high-potency antipsychotics IM (i.e. for psychiatric emergency)

Mask-like facies, resting tremor, cogwheel rigidity, shuffling gait, bradykinesia

Haloperidol
Thiothixene
Fluphenazine

Perphenazine
Loxapine

Chlorpromazine

Paliperidone
Risperidone

Asenapine
Cariprazine
Lurasidone

Aripiprazole
Brexpiprazole
Clozapine
Iloperidone
Olanzapine
Quetiapine
Ziprasidone

Anticholinergics: Mild to moderate EPS or prophylaxis
• Diphenhydramine (Benadryl)
• Benztropine (Cogentin)

However, this may worsen parkinsonian and tardive dyskenesia symptoms

All SGAs can cause significant weight gain, dyslipidemia, and insulin resistance

Increased food intake
Reduction in resting energy expenditure
Antagonism of histamine, serotonin, and dopamine receptors
Insulin homeostasis affected by serotonergic receptor blockade
Changes to neuropeptides associated with appetite control and energy metabolism (↑ leptin, ↓ adiponectin)
Genetic polymorphisms: May explain variability among patients

Clozapine
Olanzapine

Quetiapine
Iloperidone
Chlorpromazine

Risperidone
Paliperidone

Aripiprazole
Ziprasidone
Lurasidone
Asenapine
Haloperidol

Lifestyle modification (diet, exercise)
Cognitive behavioral therapy

Consider initial treatment with antipsychotics with fewer metabolic adverse effects
Switch to alternative antipsychotic if significant metabolic adverse effects occur
Adjuvant medications (Metformin, topiramate)

Complete metabolic panel required for all psychiatric inpatients discharged on an antipsychotic medication
1. BMI
2. Blood glucose or HgbA1c
3. Blood pressure
4. Lipid panel

Treat hypertension, elevated blood glucose per treatment guidelines

D2 blockade in tuberoinfundibular pathway

Gynecomastia
Galactorrhea
Menstrual disturbances
Sexual dysfunction
Infertility

Switch antipsychotic
Add aripiprazole

highest risk: FGAs
lowest risk: Quetiapine, Aripiprazole

May occur in up to 60-70% of patients treated with anipsychotics
consider alternative antipsychotic

Antagonism of histamine H1 receptors increases sedation

Most: Low potency FGAs, Clozapine
Least: Aripiprazole, Iloperidone, Palperidone

IM or IV > oral risk
QTc > 500ms = significant risk

Direct inhibition of cardiac delayed potassium rectifier

Occurs due to alpha-adrenergic blockade
most common in first few days after initiating treatment or after dose increase

Adequate hydration, salt intake
Compression stockings
Rise slowly from seated or supine positions

Divide dose of antipsychotic
Switch to antipsychotic with less antiadrenergic effects
Fludrocortisone

Antipsychotics increase risk of VTE, including pulmonary embolism (PE)
Clozapine has greatest risk, others have equal risk
Consider switching to a different antipsychotic if patient develops VTE while receiving an antipsychotic

tachycardia
constipation (very bad, patients may not realize they are constipated and could require surgery, should be given with bowel regiment)
Cholinergic agonist at M4 receptors, leads to excessive salivation, may be treated with glycopyrrolate