8.3 Psychotic Disorders & Schizophrenia Management

8.3 Psychotic Disorders & Schizophrenia Management

Psychotic disorders are characterized by abnormalities in one or more of five domains: delusions, hallucinations, disorganized thinking (speech), grossly disorganized or abnormal motor behavior (including catatonia), and negative symptoms. Prompt recognition, medical workup, and intervention are vital to optimize long-term cognitive and functional trajectories.

Spectrum of Psychotic Disorders

The psychotic spectrum is classified primarily by symptom duration and the relationship between psychotic and mood symptoms.

Duration & Diagnostic Continuum:
Brief Psychotic Disorder: < 1 month (Full recovery)
Schizophreniform Disorder: 1 month to 6 months
Schizophrenia: > 6 months (Continuous signs of disturbance, including functional decline)

Schizoaffective Disorder vs. Mood Disorder with Psychotic Features

• Schizoaffective Disorder: Major mood episode (depressive or manic) concurrent with active phase symptoms of schizophrenia, PLUS delusions or hallucinations for $\ge 2$ weeks in the absence of a major mood episode.
• Major Depressive / Bipolar Disorder with Psychotic Features: Psychotic symptoms occur exclusively during an active mood episode (manic or depressed).

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Schizophrenia: Clinical Presentation & Pathophysiology

Schizophrenia affects approximately 1% of the Canadian population, typically emerging in late adolescence or early adulthood.

Symptom Domains

1. Positive Symptoms: Excess or distortion of normal function driven by hyperdopaminergic activity in the mesolimbic pathway.
   • Delusions: Fixed, false beliefs impervious to contrary evidence (persecutory, referential, somatic, grandiose).
   • Hallucinations: Perception without external stimulus (auditory hallucinations are most common).
   • Disorganized Speech/Thinking: Derailment, loose associations, word salad, neologisms.
2. Negative Symptoms: Loss or diminution of normal function driven by hypodopaminergic activity in the mesocortical pathway.
   • The 5 A's: Avolition (lack of motivation), Alogia (poverty of speech), Anhedonia, Affective flattening, Asociality.
3. Cognitive Symptoms: Deficits in executive function, working memory, and sustained attention.

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Pharmacotherapy: First- vs. Second-Generation Antipsychotics

Antipsychotic medications form the mainstay of schizophrenia treatment.

Clozapine in Treatment-Resistant Schizophrenia (TRS)

Clozapine is the most effective antipsychotic agent available and is the gold standard for Treatment-Resistant Schizophrenia (defined as persistent symptoms despite $\ge 2$ adequate trials of different antipsychotics, at least one being an SGA).

Canadian Clozapine Monitoring Network Protocol:

• Major Life-Threatening Adverse Effect: Agranulocytosis (absolute neutrophil count [ANC] $< 1.5 \times 10^9/L$).
• Mandatory Laboratory Monitoring: Baseline Complete Blood Count (CBC) with differential, followed by weekly CBC for 6 months, biweekly for 6 months, then monthly thereafter.
• Action Thresholds: If ANC drops below $1.5 \times 10^9/L$ (mild neutropenia), increase monitoring frequency. If ANC drops below $1.0 \times 10^9/L$ (severe neutropenia/agranulocytosis), Clozapine MUST BE IMMEDIATELY DISCONTINUED and re-challenge is contraindicated.
• Other Clozapine Adverse Effects: Myocarditis/cardiomyopathy (check baseline troponin/ECG), severe constipation/paralytic ileus, sedation, hypersalivation (sialorrhea), seizures, weight gain.

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Neurological & Psychiatric Emergencies

Extrapyramidal Symptoms (EPS) & Movement Disorders

1. Acute Dystonic Reaction:
   • Timing: Hours to days after starting or increasing high-potency FGA (e.g., Haloperidol).
   • Features: Sudden involuntary contraction of muscle groups (torticollis, trismus, oculogyric crisis, laryngospasm).
   • Treatment: Intramuscular (IM) Anticholinergics — Benztropine 1–2 mg IM or Diphenhydramine 25–50 mg IM.
2. Akathisia:
   • Timing: Days to weeks after initiating antipsychotics.
   • Features: Subjective feeling of inner restlessness and objective inability to sit still (pacing, rocking).
   • Treatment: Reduce antipsychotic dose, switch to SGA, or treat with Beta-blockers (Propranolol) or Benzodiazepines.
3. Parkinsonism:
   • Timing: Weeks to months after initiation.
   • Features: Tremor (pill-rolling), rigidity (cogwheel), bradykinesia, masked facies.
   • Treatment: Add oral Benztropine or Amantadine, or switch to an SGA with low D2 affinity (e.g., Quetiapine).
4. Tardive Dyskinesia (TD):
   • Timing: Months to years of chronic antipsychotic therapy.
   • Features: Involuntary choreoathetoid movements of face, lip smacking, tongue protrusion, trunk twisting.
   • Treatment: Discontinue offending agent if possible; switch to Clozapine or Quetiapine; treat with VMAT2 Inhibitors (Valbenazine, Deutetrabenazine). Anticholinergics worsen TD!

Neuroleptic Malignant Syndrome (NMS) vs. Serotonin Syndrome

HIGH-YIELD DIFFERENTIAL DIAGNOSIS TABLE: