Quick Reference Guide: Psychiatric Medications in MAT/OTP Settings

ANTIPSYCHOTIC MEDICATIONS

First-Line Oral Antipsychotics

Haloperidol or chlorpromazine should be routinely offered as first-line agents 1. Second-generation antipsychotics may be alternatives if cost and availability permit 1.

Haloperidol

Starting dose: 2-5 mg/day
Maintenance dose: 5-20 mg/day (optimal around 5 mg/day risperidone equivalents) 2
Dosing: Once daily at night when possible 2

Chlorpromazine

Starting dose: 25-50 mg 2-3 times daily
Maintenance dose: 200-800 mg/day in divided doses
Dosing: Multiple daily doses required

Second-Generation Options (if available)

Risperidone:

Starting dose: 1-2 mg/day
Maintenance dose: 4-6 mg/day
Dosing: Once or twice daily

Olanzapine:

Starting dose: 5-10 mg/day
Maintenance dose: 10-20 mg/day
Dosing: Once daily at bedtime
Critical caveat: Co-prescribe metformin to attenuate weight gain 3

Aripiprazole:

Starting dose: 10-15 mg/day
Maintenance dose: 15-30 mg/day
Dosing: Once daily

Quetiapine:

Starting dose: 25-50 mg twice daily
Maintenance dose: 300-800 mg/day in divided doses

Treatment Algorithm for Psychosis

First trial (4 weeks minimum at therapeutic dose): Haloperidol or second-generation antipsychotic 3
If inadequate response after 4 weeks: Switch to alternative with different pharmacodynamic profile (e.g., if started D2 partial agonist, switch to amisulpride, risperidone, paliperidone, or olanzapine) 3
If second trial fails (another 4 weeks): Reassess diagnosis, rule out substance use/organic causes, then initiate clozapine 3

Clozapine (treatment-resistant cases only):

Starting dose: 12.5 mg once or twice daily
Titration: Increase by 25-50 mg/day
Target dose: Sufficient to achieve plasma level ≥350 ng/mL 3
Maintenance dose: 300-600 mg/day (individualized to plasma levels)
Mandatory: Co-prescribe metformin; requires routine laboratory monitoring 1, 3

Duration of Treatment

Continue antipsychotic for minimum 12 months after remission 1
Withdrawal after several stable years may be considered with mental health specialist consultation 1

LONG-ACTING INJECTABLE (LAI) ANTIPSYCHOTICS FOR MAT/OTP SETTINGS

Patients on long-term antipsychotic treatment should be offered choice between oral and depot preparations to improve adherence 1. LAIs are particularly valuable in OTP settings where adherence monitoring is critical 4, 5.

Evidence-Based Indications for LAIs in OTP Settings

Initiate LAIs proactively and early after confirmed diagnosis 5, 6:

After first psychotic episode with adherence concerns
Before multiple relapses occur (not as last resort) 5, 6
When oral adherence is uncertain or demonstrated to be problematic
To assess true treatment resistance vs. non-adherence 5

First-Generation LAI Options

Haloperidol Decanoate

Test dose: 25-50 mg IM
Starting dose: 50-100 mg IM every 4 weeks
Maintenance dose: 50-300 mg IM every 4 weeks
Oral overlap: Continue oral haloperidol for 3-4 weeks after first injection 7

Fluphenazine Decanoate

Starting dose: 12.5-25 mg IM every 2-3 weeks
Maintenance dose: 12.5-100 mg IM every 2-4 weeks
Oral overlap: Continue oral antipsychotic for 2-3 weeks 7

Second-Generation LAI Options

Risperidone Microspheres (Risperdal Consta)

Starting dose: 25 mg IM every 2 weeks
Maintenance dose: 25-50 mg IM every 2 weeks
Critical: Mandatory oral risperidone supplementation for 21 days after first injection 7, 8
Dosing window: Can administer up to +14 days late; if exceeded, restart oral supplementation for 21 days 8

Paliperidone Palmitate (Invega Sustenna - monthly)

Day 1: 234 mg IM deltoid
Day 8: 156 mg IM deltoid
Maintenance (monthly): 117 mg IM deltoid or gluteal every 4 weeks (range 78-234 mg)
No oral supplementation required 7
Dosing window: +14 days; if exceeded, follow catch-up protocol based on time elapsed 8

Paliperidone Palmitate (Invega Trinza - 3-monthly)

Prerequisite: Stable on monthly paliperidone for ≥4 months
Conversion: 3.5× the monthly dose, given every 3 months
Example: 117 mg monthly → 410 mg every 3 months

Aripiprazole Monohydrate (Abilify Maintena)

Day 1: 400 mg IM with 20 mg oral aripiprazole
Maintenance: 400 mg IM monthly
Oral overlap: Continue oral aripiprazole 20 mg daily for 14 days 7, 8
Dosing window: ±7 days; if exceeded, restart with oral supplementation for 14 days 8

Aripiprazole Lauroxil (Aristada)

Starting dose: 441 mg, 662 mg, or 882 mg IM monthly (or 882 mg every 6 weeks)
Initiation options:
- With 21 days oral aripiprazole, OR
- With single 675 mg Aristada Initio injection (no oral needed)
Maintenance: Continue chosen dose at chosen interval

MOOD STABILIZERS

Bipolar Mania

Haloperidol is recommended for acute mania 1. Lithium, valproate, or carbamazepine should be offered 1.

Lithium

Starting dose: 300 mg twice daily
Maintenance dose: 900-1800 mg/day in divided doses
Target level: 0.6-1.2 mEq/L (acute); 0.6-0.8 mEq/L (maintenance)
Critical: Initiate only where close clinical and laboratory monitoring available 1
Monitoring: Baseline and periodic: renal function (Cr, BUN, eGFR), thyroid (TSH, free T4), calcium, ECG if >50 years or cardiac risk factors
Frequency: Lithium level weekly until stable, then every 3-6 months; renal/thyroid every 6-12 months

Valproate/Divalproex

Starting dose: 250 mg twice daily
Maintenance dose: 750-2000 mg/day in divided doses
Target level: 50-125 mcg/mL
Monitoring: Baseline LFTs, CBC, pregnancy test; repeat LFTs at 1 month, then every 6-12 months
Critical caveat: Avoid in women of childbearing potential if possible 1

Carbamazepine

Starting dose: 200 mg twice daily
Maintenance dose: 600-1200 mg/day in divided doses
Target level: 4-12 mcg/mL
Monitoring: Baseline CBC, LFTs, sodium; repeat CBC/LFTs at 1 month, then every 3-6 months
Drug interactions: Strong CYP450 inducer—reduces levels of aripiprazole, risperidone, methadone, buprenorphine 8, 9

Bipolar Maintenance

Lithium or valproate should be used for maintenance treatment for minimum 2 years after last episode 1. Continue same dosing as acute phase.

Bipolar Depression

Antidepressants must always be combined with mood stabilizer (lithium or valproate) 1. SSRIs (fluoxetine) preferred over tricyclics 1.

ANTIDEPRESSANTS

SSRIs (First-Line)

Fluoxetine

Starting dose: 10-20 mg daily
Maintenance dose: 20-60 mg daily
Dosing: Once daily, morning
Caveat: CYP450 inhibitor—increases levels of aripiprazole, risperidone 8

Sertraline

Starting dose: 25-50 mg daily
Maintenance dose: 50-200 mg daily
Dosing: Once daily

Escitalopram

Starting dose: 5-10 mg daily
Maintenance dose: 10-20 mg daily
Dosing: Once daily

SNRIs

Venlafaxine

Starting dose: 37.5-75 mg daily
Maintenance dose: 75-225 mg daily 10
Dosing: Once or twice daily

Duloxetine

Starting dose: 30-60 mg daily
Maintenance dose: 60-120 mg daily 10
Dosing: Once daily

Tricyclic Antidepressants (Second-Line)

Nortriptyline (preferred TCA—better tolerated)

Starting dose: 10-25 mg nightly
Maintenance dose: 50-150 mg nightly 10
Target level: 50-150 ng/mL
Monitoring: Baseline ECG if >40 years or cardiac history; repeat if dose >100 mg

Desipramine

Starting dose: 10-25 mg nightly
Maintenance dose: 50-150 mg nightly 10
Target level: 125-300 ng/mL

Other Antidepressants

Bupropion

Starting dose: 100-150 mg daily
Maintenance dose: 150-450 mg daily 10
Dosing: Divided doses or extended-release once daily
Contraindication: Seizure disorder, eating disorders

Mirtazapine

Starting dose: 7.5-15 mg nightly
Maintenance dose: 15-45 mg nightly
Benefit: Useful for akathisia management 8

ANXIOLYTICS/SEDATIVES

Benzodiazepines (Use with Extreme Caution in OTP Settings)

Critical safety concern: Combined use with opioids significantly increases overdose risk 9, 11. Avoid if possible; if necessary, use lowest effective dose with close monitoring.

Lorazepam (preferred—no active metabolites)

Starting dose: 0.5-1 mg 2-3 times daily
Maximum dose: 6 mg/day
Taper: Reduce by 10-25% every 1-2 weeks when discontinuing

Clonazepam

Starting dose: 0.25-0.5 mg twice daily
Maximum dose: 4 mg/day

Non-Benzodiazepine Alternatives

Hydroxyzine

Dose: 25-100 mg 3-4 times daily as needed
Safer option in OTP settings

Gabapentin (off-label for anxiety)

Starting dose: 100-300 mg nightly
Maintenance dose: 900-1800 mg/day in divided doses 10

SPECIAL CONSIDERATIONS FOR MAT/OTP SETTINGS

Drug-Drug Interactions with Opioid Agonist Therapy

Methadone interactions:

Carbamazepine: Reduces methadone levels—may precipitate withdrawal 9
Fluvoxamine, fluoxetine: Increase methadone levels—monitor for sedation 9
Benzodiazepines: Additive CNS depression—avoid if possible 9, 11

Buprenorphine interactions:

Carbamazepine: Reduces buprenorphine levels 9
Benzodiazepines: Respiratory depression risk—avoid 9, 11

Perioperative Management in OTP Patients

Continue MOUD throughout perioperative period 9. Do not withhold methadone or buprenorphine for surgery. Adjust opioid analgesics accordingly—patients on MOUD require higher opioid doses for acute pain.

Pregnancy and Breastfeeding in OTP Settings

Do not discontinue MOUD during pregnancy 9. Methadone and buprenorphine are safe and reduce maternal/fetal morbidity. For psychiatric medications:

Avoid valproate in women of childbearing potential 1
Lithium: Requires careful monitoring but not absolutely contraindicated
Antipsychotics: Continue if needed; benefits typically outweigh risks
Breastfeeding: Compatible with phenobarbital, phenytoin, carbamazepine, valproic acid 1; most antipsychotics and antidepressants

SAFETY MONITORING PARAMETERS

Antipsychotics

Baseline (before initiation):

Weight, BMI, waist circumference
Blood pressure, pulse
Fasting glucose, HbA1c
Lipid panel (total cholesterol, LDL, HDL, triglycerides)
CBC (for clozapine: mandatory ANC)
LFTs
Pregnancy test if applicable
ECG if risk factors or using QTc-prolonging agent

Ongoing monitoring:

Weight/BMI: Monthly for 3 months, then quarterly
Glucose/HbA1c: 3 months, then annually (more frequently if prediabetic/diabetic)
Lipids: 3 months, then annually
Blood pressure: Every visit initially, then quarterly
Movement disorders: Every visit (use AIMS scale quarterly)
Clozapine ANC: Weekly for 6 months, then biweekly for 6 months, then monthly

Mood Stabilizers

Lithium:

Level: Weekly until stable, then every 3-6 months
Renal function (Cr, BUN, eGFR): Baseline, 3 months, then every 6-12 months
Thyroid (TSH, free T4): Baseline, 6 months, then every 6-12 months
Calcium: Baseline, then annually
ECG: Baseline if >50 years or cardiac risk factors

Valproate:

Level: After dose changes, then every 6-12 months
LFTs: Baseline, 1 month, then every 6-12 months
CBC with platelets: Baseline, then every 6-12 months
Pregnancy test: Baseline and periodically if childbearing potential

Carbamazepine:

Level: After dose changes, then every 6-12 months
CBC: Baseline, 1 month, then every 3-6 months
LFTs: Baseline, 1 month, then every 3-6 months
Sodium: Baseline, then every 6-12 months

Antidepressants

TCAs:

ECG: Baseline if >40 years or cardiac history; repeat if dose >100 mg or symptoms
Level: If suboptimal response or toxicity concerns

All antidepressants:

Monitor for activation, suicidality (especially first 4 weeks)
Blood pressure monitoring with SNRIs

MANAGEMENT OF COMMON SIDE EFFECTS

Extrapyramidal Symptoms (EPS)

Do not use anticholinergics routinely for prevention 1. Use only when:

Dose reduction ineffective
Switching strategies ineffective
Symptoms acute or severe 1

Benztropine:

Dose: 0.5-2 mg twice daily
Short-term use only

Trihexyphenidyl:

Dose: 1-2 mg 2-3 times daily

Akathisia

First-line: Reduce antipsychotic dose 8

Adjunctive options (until dose adjustment reaches steady state):

Vitamin B6: 600-1200 mg daily 8
Mirtazapine: 7.5-15 mg nightly 8
Propranolol: 10-30 mg 2-3 times daily (if no contraindications)

Weight Gain/Metabolic Effects

Metformin co-prescription with olanzapine or clozapine 3:

Starting dose: 500 mg twice daily with meals
Maintenance dose: 1000 mg twice daily
Titrate gradually to minimize GI side effects

Sedation

Strategies:

Administer entire dose at bedtime when possible 2
Consider dose reduction
Switch to less sedating agent
Adjunctive stimulants (if sedation persists):
- Caffeine 100-200 mg every 4 hours 10
- Methylphenidate 5-10 mg 1-3 times daily (morning/early afternoon only) 10
- Modafinil 100-200 mg daily 10

PRACTICAL ALGORITHMS

Switching Between Antipsychotics

Cross-titration approach (preferred):

Start new antipsychotic at low dose
Gradually increase new agent to therapeutic dose over 1-2 weeks
Simultaneously taper old agent by 25% every 3-7 days
Consider receptor profiles and half-lives when determining taper speed 3

Exceptions requiring abrupt switch:

Clozapine to another agent (due to agranulocytosis risk)
Severe adverse reaction

Oral to LAI Conversion

General principles 7, 12:

Establish oral tolerability first (except paliperidone palmitate)
Provide oral supplementation as specified for each LAI
Schedule follow-up within dosing window
Implement reminder systems (calls, texts) 8
Involve family/caregivers in adherence plan 8

Managing Missed LAI Doses

Within dosing window:

Administer as soon as possible 8

Beyond dosing window:

Aripiprazole (>±7 days): Restart oral supplementation for 14 days 8
Risperidone (>+14 days): Restart oral supplementation for 21 days 8
Paliperidone (>+14 days): Follow manufacturer catch-up protocol based on time elapsed 8

Assessing Treatment Resistance

Criteria:

Two adequate trials of different antipsychotics (4 weeks each at therapeutic dose with confirmed adherence) 3
Persistent significant positive symptoms
Diagnosis confirmed, organic causes excluded
Then: Initiate clozapine trial 3

KEY PITFALLS TO AVOID

Do not reserve LAIs for treatment failures—consider proactively and early 5, 6
Do not combine benzodiazepines with opioid agonist therapy unless absolutely necessary with intensive monitoring 9, 11
Do not use anticholinergics prophylactically for EPS 1
Do not prescribe valproate to women of childbearing potential without serious consideration of alternatives 1
Do not discontinue MOUD perioperatively or during pregnancy 9
Do not forget oral supplementation when initiating risperidone or aripiprazole LAIs 7, 8
Do not exceed maximally effective doses—approximately 5 mg/day risperidone equivalents for most antipsychotics 2
Do not initiate lithium without laboratory monitoring capacity 1
Do not forget metformin co-prescription with olanzapine or clozapine 3
Do not ignore drug interactions between carbamazepine and methadone/buprenorphine 8, 9

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