Psychosocial, Behavioral & Cognitive · Topic 8 of 8

Bipolar Disorder, Psychosis & Antipsychotic Monitoring

Tap any line to see why it matters

Psychosocial · bipolar and psychotic disorders

Bipolar Disorder, Psychosis & Antipsychotic Monitoring

Mania lasts at least a week (less if hospitalized) and is treated with lithium, divalproex or a second-generation antipsychotic. Every antipsychotic needs metabolic and tardive dyskinesia monitoring.

01 · Mania defined≥ 1 week (less if hospitalized) + ≥ 3 symptoms

02 · First moveLithium, divalproex or 2nd-gen antipsychotic

03 · Every antipsychoticWeight, BP, glucose, lipids: baseline, 12 weeks

Why bipolar disorder happens

Heritable, with drug and substance triggers

Neurotransmitter dysregulation; drugs and substances can trigger episodes

The exact cause is unknown; heritability is 70–90%. Triggers include sympathomimetics, alcohol, corticosteroids and some antidepressants (tricyclics, noradrenergic reuptake inhibitors).

Exclude first

Rule out drugs and medical causes before naming a psychiatric disorder

Stimulant use: order a toxicology screen

Corticosteroids or dopamine agonists as the cause

Hyperthyroidism: order T4 and TSH

Order CBC and metabolic panel

Test for pheochromocytoma only with marked hypertension

New psychosis: exclude medical and substance causes

Use history, examination, laboratory tests and neuroimaging

No laboratory or imaging test diagnoses schizophrenia itself

For acute fluctuating confusion, see Delirium.

Diagnosis: bipolar disorder

Bipolar I needs mania; bipolar II needs hypomania plus depression

Mania: elevated, expansive or irritable mood with increased energy

Mania lasts ≥ 1 week, or less if hospitalized

Mania adds ≥ 3 symptoms, or ≥ 4 if mood is only irritable

Mania causes severe impairment, psychosis or hospitalization

Bipolar I: at least 1 manic episode

Bipolar II: ≥ 1 hypomanic and ≥ 1 major depressive episode, no mania

Hypomania: ≥ 4 days, no psychosis, marked impairment or hospitalization

Diagnosis: schizophrenia

≥ 2 characteristic symptoms for at least 1 month

At least 1 is delusions, hallucinations or disorganized speech

Functional decline

Continuous signs of illness for at least 6 months

Red flags

Ask every patient directly about suicidal ideation, plans or activity ask directly

15–20% with bipolar disorder die by suicide, about 20–60 times the general rate

Fever, rigidity, altered mental status, autonomic instability on an antipsychotic suspect NMS, stop drug

Laryngeal dystonia: IV lorazepam, possibly intubate IV lorazepam

Antidepressant as sole therapy for bipolar depression do not use alone

IM olanzapine with a parenteral benzodiazepine do not combine

See Suicide Risk, Neuroleptic Malignant Syndrome, and Acute Agitation & Restraints.

First moves in acute mania

Exclude stimulants, corticosteroids, dopamine agonists, hyperthyroidism

Severe manic psychosis: sedating second-generation antipsychotic now

Treat mania: lithium, divalproex or a second-generation antipsychotic

Treatment

Maniaacute treatment

Lithium Divalproex Quetiapine Aripiprazole Asenapine Paliperidone Cariprazine

Lithium, divalproex or a second-generation antipsychotic

Lithium takes 4–10 days: add a faster agent for significant symptoms

Severemanic psychosis

Sedating 2nd-gen antipsychotic Lorazepam or clonazepam, sometimes Haloperidol IM

Sedating second-generation antipsychotic for urgent control

IM haloperidol is an option for extreme hyperactivity with poor food and fluid intake

Depressionbipolar, first-line options

Quetiapine Lurasidone + lithium or divalproex Lithium Lamotrigine Cariprazine

Quetiapine for bipolar II

Never an antidepressant as sole therapy

Metabolic riskprefer these agents

Lurasidone Cariprazine Lumateperone Ziprasidone Aripiprazole

For patients with or at risk of metabolic syndrome

Second-generation agents: less tardive dyskinesia, more metabolic syndrome than first-generation

Maintenance, first-episode relapse, carbamazepine, xanomeline-trospium

Bipolar I in remission: maintenance for all patientsMood stabilizer or antipsychotic. More than half may not fully adhere, so explore adherence when episodes recur

First psychotic episode: continue at least 1–2 yearsWithout ongoing antipsychotic treatment, 65–80% relapse within 12 months

Carbamazepine gets no loading doseScreen patients of at-risk Asian ancestry for HLA-B*1502 (SJS/TEN); watch for aplastic anemia and agranulocytosis

Xanomeline-trospium: no effect on dopamine D2 receptorsA muscarinic agonist with a peripheral anticholinergic; the first antipsychotic with no D2 effect

Monitor every long-term antipsychotic

ADA/APA schedule, plus AIMS at least every 6 months

Baseline: weight, waist, BP, fasting glucose or A1c, lipids

Weight at 4, 8 and 12 weeks, then every 3 months

BP, glucose and lipids at 12 weeks, then yearly

AIMS for tardive dyskinesia at least every 6 months

First-generation agents: tardive dyskinesia risk up about 5% per year of exposure

The 2004 consensus rechecked lipids every 5 years; current summaries prefer yearly, keeping 5 years for lower cardiovascular risk. The 2020 APA schizophrenia guideline individualizes the interval to the drug and the patient.

Movement effects

Tardive dyskinesia: VMAT2 inhibitor, valbenazine or deutetrabenazine

Tardive dyskinesia may persist indefinitely after the antipsychotic stops

Still needs an antipsychotic with tardive dyskinesia: clozapine or quetiapine

Acute dystonia: IV or IM benztropine or diphenhydramine give IV or IM

Akathisia: lower the dose or switch agents, or add propranolol

Clozapine

Reserved for inadequate response to other antipsychotics; reduces suicidality

Start only with ANC ≥ 1500/µL (≥ 1000/µL with benign ethnic neutropenia)

ANC weekly for 6 months, every 2 weeks for 6 months, then monthly

ANC 500–999/µL: interrupt, except in benign ethnic neutropenia interrupt

ANC below 500/µL: discontinue clozapine discontinue

Fatal myocarditis, dose-related seizures, orthostatic hypotension

Severe GI hypomotility: treat constipation promptly

FDA removed the clozapine REMS effective June 13, 2025: prescribers no longer report ANC to a program, but label monitoring continues. With benign ethnic neutropenia, 500–999/µL continues with hematology consultation and testing three times weekly.

Lithium

Lithium target level 0.6–1.2 mEq/L

Level every 6 months and with dose changes

TSH before starting, then every 1–2 years

BUN and creatinine 1–2 times yearly after the first 6 months

The lithium label gives 0.8–1.2 mEq/L for the acute phase and 0.6–1.2 mEq/L for long-term control. Toxicity, interactions and dialysis criteria are on the Lithium Toxicity sheet.

Divalproex and lamotrigine

Divalproex for mania: start 750 mg daily or load 20–30 mg/kg

Mania trough 50–125 mcg/mL (50–100 mcg/mL is the epilepsy target)

Divalproex boxed warnings: hepatotoxicity, fetal harm, pancreatitis

Unexplained lethargy, vomiting or confusion on divalproex check ammonia

Lamotrigine is for maintenance and depression, not acute mania

Boxed Stevens-Johnson warning: risk rises with fast titration and valproate

Most serious lamotrigine rashes appear within 2–8 weeks

Mania or hypomania?

	Mania	Hypomania
Duration	≥ 1 week, or less if hospitalized	≥ 4 days
Psychosis	May be present	Absent
Function	Severe impairment	No marked impairment
Hospitalization	May be needed	Not needed
Defines	Bipolar I	Bipolar II, with a major depressive episode

Pearl

Hypomania four days, mania one week; every long-term antipsychotic earns metabolic labs and an AIMS.

Sources · Merck Manual Professional — Bipolar Disorders · Merck Manual Professional — Medications for Treatment of Bipolar Disorders · Merck Manual Professional — Antipsychotic Medications · NY State Medicaid Prescriber Education Program — Metabolic Monitoring of Antipsychotic Medications (adapted from the ADA/APA consensus), 2024 · Merck Manual Professional — Schizophrenia · DailyMed — Lithium carbonate label · DailyMed — Divalproex sodium delayed-release tablets label · DailyMed — Lamotrigine tablets label · DailyMed — Clozapine tablets label · FDA Drug Safety Communication — FDA removes REMS program for clozapine (2025) · DailyMed — Carbamazepine extended-release tablets label · Psychiatric Times — Metabolic Monitoring for Patients on Antipsychotic Medications · Follow your institution's protocols.