By James Aspinwall, co-written by Alfred Pennyworth (my trusted AI) — February 27, 2026, 22:05
Based on the clinical compendium authored by K. Aspinwall Millett, PMHNP, FNP, DNP
Karen Aspinwall Millett’s psychiatric pharmacology compendium is built for the clinician standing in front of a patient, not the student sitting in a lecture hall. It organizes adult psychiatric medications by clinical use, flags the interactions that actually hurt people, and structures monitoring requirements so nothing falls through the cracks.
This review walks through the compendium’s core content and addresses the key requirements for a prescriber-ready reference: references, organization, medication accuracy, interaction nuances, and clinical safety alerts.
1. Pharmacology Foundations
The compendium opens with the distinction every prescriber must internalize:
- Pharmacokinetics — what the body does to the drug: absorption, distribution, metabolism, excretion
- Pharmacodynamics — what the drug does to the body: receptor binding, ion channel modulation, downstream effects
CYP450 Enzymes: The Interaction Engine
The cytochrome P450 system is where most dangerous drug interactions originate. The compendium correctly identifies this as foundational knowledge:
Inhibitors slow drug metabolism, raising plasma levels toward toxicity:
- Bupropion — potent CYP2D6 inhibitor. Co-prescribing with drugs metabolized by 2D6 (e.g., many antipsychotics, some beta-blockers) can push levels dangerously high [^1]
- Fluoxetine and Paroxetine — also strong CYP2D6 inhibitors, often overlooked when added to existing regimens [^2]
- Fluvoxamine — potent CYP1A2 inhibitor, critically important when combined with Clozapine or Olanzapine [^3]
Inducers accelerate metabolism, dropping levels below therapeutic thresholds:
- Carbamazepine — broad inducer (CYP3A4, 1A2, 2C9), can render oral contraceptives, Lamotrigine, and many other medications ineffective [^4]
- Smoking (polycyclic aromatic hydrocarbons) — induces CYP1A2, directly affecting Clozapine and Olanzapine levels. When a patient quits smoking, levels can spike 50-70% without dose adjustment [^5]
Renal Clearance — The Lithium-NSAID Trap: NSAIDs (ibuprofen, naproxen) reduce renal prostaglandin synthesis, decreasing lithium clearance by 15-25%. This is one of the most common pathways to lithium toxicity in outpatient practice. ACE inhibitors and thiazide diuretics carry similar risks [^6].
Prescriber Alert: Every patient on lithium should be explicitly warned about over-the-counter NSAIDs. This is not a theoretical interaction — it sends patients to emergency departments regularly.
2. ADHD Medications
Stimulants (Schedule II)
Treatment typically begins with stimulants, titrated from low doses:
| Medication | Generic | Mechanism | Duration | Key Notes |
|---|---|---|---|---|
| Adderall | Mixed amphetamine salts | DA/NE release | 4-6h (IR), 10-12h (XR) | Available as IR and XR; generic widely available |
| Adderall XR | Mixed amphetamine salts | DA/NE release | 10-12h | Capsule can be opened and sprinkled |
| Ritalin | Methylphenidate | DA/NE reuptake inhibitor | 3-4h (IR) | Short-acting; useful for dose titration |
| Concerta | Methylphenidate ER | DA/NE reuptake inhibitor | 10-12h | OROS delivery system; do not crush |
| Vyvanse | Lisdexamfetamine | Prodrug → d-amphetamine | 10-14h | Lower abuse potential (requires enzymatic conversion); FDA-approved for BED |
| Mydayis | Mixed amphetamine salts | DA/NE release | Up to 16h | Triple-bead extended release |
Side effects common to stimulants: appetite suppression, insomnia, increased heart rate/blood pressure, anxiety, potential for abuse.
Interactions:
- MAOIs — absolutely contraindicated; risk of hypertensive crisis [^7]
- Acidifying agents (ascorbic acid, citrus) — decrease amphetamine absorption
- Alkalinizing agents (sodium bicarbonate) — increase amphetamine absorption and prolong effects
Non-Stimulants
Used when substance abuse risk is present, stimulants are not tolerated, or as adjuncts:
| Medication | Generic | Mechanism | Key Notes |
|---|---|---|---|
| Strattera | Atomoxetine | Selective NE reuptake inhibitor | FDA black box: suicidal ideation in children/adolescents; metabolized by CYP2D6 — watch for interactions with 2D6 inhibitors [^8] |
| Intuniv | Guanfacine ER | Alpha-2A agonist | Sedation common initially; do not discontinue abruptly (rebound hypertension) |
| Qelbree | Viloxazine ER | NE reuptake inhibitor / 5-HT modulator | Newer option; can increase levels of CYP1A2 substrates; avoid with MAOIs [^9] |
3. Antidepressants
SSRIs — First-Line for MDD, OCD, GAD
| Medication | Starting Dose | CYP Interactions | Unique Considerations |
|---|---|---|---|
| Fluoxetine (Prozac) | 10-20 mg | Strong 2D6 inhibitor | Longest half-life (2-6 days; norfluoxetine 4-16 days); least withdrawal risk; can remain active weeks after discontinuation [^10] |
| Sertraline (Zoloft) | 25-50 mg | Mild 2D6 inhibitor | Best studied in cardiac patients; take with food for absorption [^11] |
| Escitalopram (Lexapro) | 5-10 mg | Minimal CYP interactions | Cleanest pharmacokinetic profile of SSRIs; dose-dependent QTc prolongation above 20 mg [^12] |
| Paroxetine (Paxil) | 10-20 mg | Strong 2D6 inhibitor | Highest anticholinergic load among SSRIs; worst withdrawal syndrome; avoid in pregnancy (category D) [^13] |
| Citalopram (Celexa) | 10-20 mg | Mild CYP interactions | FDA max 40 mg (20 mg if >60 years or hepatic impairment) due to QTc risk [^14] |
| Fluvoxamine (Luvox) | 25-50 mg | Strong 1A2, 2C19 inhibitor | Primary use: OCD; most drug interactions of any SSRI |
Class-wide alerts:
- Serotonin syndrome — risk with any combination of serotonergic agents (tramadol, triptans, linezolid, St. John’s Wort) [^15]
- Bleeding risk — SSRIs inhibit platelet serotonin uptake; increased risk with concurrent NSAIDs or anticoagulants [^16]
- Hyponatremia/SIADH — higher risk in elderly; monitor sodium if new confusion or falls [^17]
- Sexual dysfunction — affects 30-70% of patients; most common reason for non-adherence
- Discontinuation syndrome — worst with paroxetine and venlafaxine (short half-lives); taper gradually
Food interaction: Grapefruit juice inhibits CYP3A4 in the gut wall. While SSRIs are primarily metabolized by CYP2D6/2C19, any co-prescribed medications metabolized by 3A4 (e.g., benzodiazepines like alprazolam, some statins) may be affected [^18].
SNRIs — Dual Reuptake Inhibition
| Medication | Mechanism | Unique Considerations |
|---|---|---|
| Venlafaxine (Effexor XR) | 5-HT > NE reuptake inhibitor | Dose-dependent: serotonergic at low doses, noradrenergic at ≥150 mg; monitor blood pressure; severe discontinuation syndrome [^19] |
| Duloxetine (Cymbalta) | Balanced 5-HT/NE reuptake inhibitor | FDA-approved for neuropathic pain, fibromyalgia, chronic musculoskeletal pain; avoid in hepatic impairment; CYP2D6 inhibitor [^20] |
| Desvenlafaxine (Pristiq) | Active metabolite of venlafaxine | Fewer CYP interactions (not dependent on 2D6 for activation); fixed dosing |
| Levomilnacipran (Fetzima) | NE > 5-HT reuptake inhibitor | More noradrenergic; monitor heart rate and blood pressure; urinary hesitancy possible |
TCAs — Older but Not Obsolete
Tricyclics boost serotonin and norepinephrine by blocking reuptake transporters, but their side effect burden limits first-line use:
- Amitriptyline (Elavil) — pain syndromes, migraine prophylaxis, insomnia; highly anticholinergic
- Nortriptyline (Pamelor) — better tolerated than amitriptyline; therapeutic drug monitoring available (target: 50-150 ng/mL)
- Desipramine — most noradrenergic TCA; least sedating; cardiac risk at overdose
Critical safety note: TCAs are lethal in overdose (cardiac arrhythmia, seizures). A one-week supply can be a fatal dose. Prescribe limited quantities in suicidal patients [^21].
Interactions:
- CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) can double or triple TCA levels
- Anticholinergic stacking with antihistamines, bladder medications, and over-the-counter sleep aids
- Alcohol potentiates CNS depression and sedation
Other Antidepressants
| Medication | Class | Key Notes |
|---|---|---|
| Bupropion (Wellbutrin) | NDRI | No sexual dysfunction; lowers seizure threshold (contraindicated in eating disorders, seizure history); potent CYP2D6 inhibitor; smoking cessation aid (Zyban) [^22] |
| Mirtazapine (Remeron) | NaSSA | Sedating at lower doses (15 mg > 30 mg for sedation due to antihistamine predominance); appetite stimulant; useful in underweight or insomniac patients; minimal sexual side effects [^23] |
| Trazodone (Desyrel) | SARI | Primarily used off-label for insomnia at 25-100 mg; priapism risk (rare but medical emergency); orthostatic hypotension |
| Esketamine (Spravato) | NMDA antagonist | Nasal spray for treatment-resistant depression; REMS program required; must be administered in certified healthcare settings with 2-hour monitoring [^24] |
Alcohol and antidepressants: All antidepressants carry additive CNS depression with alcohol. Beyond sedation, alcohol is a depressant that directly undermines treatment efficacy. Patients should be counseled clearly, not just handed a warning label.
4. Antipsychotics
First Generation (Typical) — D2 Antagonists
| Medication | Potency | Key Considerations |
|---|---|---|
| Haloperidol (Haldol) | High | EPS risk highest; available IM/IV for acute agitation; decanoate form for long-acting injection; QTc prolongation with IV use [^25] |
| Fluphenazine | High | Available as decanoate (long-acting injection q2-4 weeks); high EPS risk |
| Chlorpromazine (Thorazine) | Low | More sedating, more anticholinergic, less EPS; photosensitivity; orthostatic hypotension |
| Perphenazine | Medium | Used in CATIE trial; moderate side effect profile |
EPS spectrum: acute dystonia → akathisia → parkinsonism → tardive dyskinesia (with chronic use)
Second Generation (Atypical) — Serotonin-Dopamine Antagonists
| Medication | Key Considerations |
|---|---|
| Risperidone (Risperdal) | Dose-dependent EPS (higher doses approach typical profile); prolactin elevation highest in class; available as long-acting injection (Risperdal Consta) [^26] |
| Olanzapine (Zyprexa) | Most weight gain and metabolic risk in class; highly effective for acute mania and psychosis; smoking induces CYP1A2 metabolism [^27] |
| Quetiapine (Seroquel) | Sedating; used off-label for insomnia (low dose) and adjunct for MDD (150-300 mg); metabolic effects; orthostatic hypotension |
| Aripiprazole (Abilify) | Partial D2 agonist; least metabolic risk; akathisia common; weight-neutral; available as long-acting injection (Maintena, Aristada) [^28] |
| Ziprasidone (Geodon) | Must take with food (500+ calories for absorption); QTc prolongation risk; weight-neutral |
| Lurasidone (Latuda) | Must take with food (350+ calories); FDA-approved for bipolar depression; favorable metabolic profile [^29] |
| Cariprazine (Vraylar) | D3-preferring partial agonist; long half-life (2-4 weeks for active metabolite); FDA-approved for bipolar depression and schizophrenia |
| Clozapine (Clozaril) | Gold standard for treatment-resistant schizophrenia; requires REMS enrollment and absolute neutrophil count (ANC) monitoring — risk of agranulocytosis (1-2%); seizure risk dose-dependent; myocarditis risk in first month; metabolic effects significant; CYP1A2 substrate (smoking and fluvoxamine interactions critical) [^30] |
Prescriber Alert — Clozapine and smoking: A patient on stable Clozapine who quits smoking (or is hospitalized where they can’t smoke) can experience a rapid, dangerous rise in Clozapine levels. Dose reduction of 30-50% may be needed. Conversely, a patient who starts smoking may drop below therapeutic levels [^5].
Metabolic monitoring for all atypical antipsychotics:
- Baseline and periodic: fasting glucose, lipid panel, HbA1c, weight/BMI, waist circumference
- Blood pressure at each visit
- ANC monitoring for Clozapine per REMS schedule
5. Mood Stabilizers
| Medication | Mechanism | Monitoring | Key Notes |
|---|---|---|---|
| Lithium | Multiple (GSK-3 inhibition, neuroprotection) | Serum levels (0.6-1.2 mEq/L), renal function (Cr, BUN), thyroid (TSH q6mo), calcium | Gold standard for bipolar disorder; only medication proven to reduce suicide risk; narrow therapeutic index [^31] |
| Valproic Acid (Depakote) | GABA enhancement, sodium channel | Serum levels (50-125 mcg/mL), LFTs, CBC with platelets | Teratogenic (neural tube defects — absolute contraindication in pregnancy/women of childbearing age without reliable contraception); weight gain; thrombocytopenia; pancreatitis risk [^32] |
| Carbamazepine (Tegretol) | Sodium channel blocker | Serum levels (4-12 mcg/mL), CBC, LFTs, sodium | Auto-induces its own metabolism (levels drop over weeks); HLA-B*1502 screening in Asian patients (Stevens-Johnson Syndrome risk); broad CYP inducer [^33] |
| Lamotrigine (Lamictal) | Glutamate modulation | No blood levels needed | Must titrate slowly (risk of Stevens-Johnson Syndrome, especially if combined with valproate which doubles lamotrigine levels); first-line for bipolar depression; weight-neutral [^34] |
| Oxcarbazepine (Trileptal) | Sodium channel blocker | Sodium levels | Less CYP induction than carbamazepine; hyponatremia risk higher in elderly |
Lithium toxicity triad: tremor → ataxia/confusion → seizures/renal failure
Substances that raise lithium levels:
- NSAIDs (ibuprofen, naproxen) — most common culprit
- ACE inhibitors, ARBs
- Thiazide diuretics
- Dehydration, low-sodium diet, excessive sweating
Prescriber Alert: Patients on lithium in tropical or physically active environments (athletes, outdoor workers) are at elevated risk during hot weather. Dehydration and sodium loss through sweat directly increase lithium levels.
6. Anxiolytics
Benzodiazepines (Schedule IV)
| Medication | Onset | Half-Life | Key Notes |
|---|---|---|---|
| Alprazolam (Xanax) | Fast | Short (6-12h) | Highest abuse potential in class; interdose rebound anxiety; difficult to taper |
| Lorazepam (Ativan) | Intermediate | Intermediate (10-20h) | No active metabolites; safest in hepatic impairment (glucuronidation only); available IM/IV [^35] |
| Clonazepam (Klonopin) | Intermediate | Long (18-50h) | Less interdose rebound; used for panic disorder, seizures |
| Diazepam (Valium) | Fast | Very long (20-100h with active metabolites) | Accumulates in elderly; muscle relaxant properties |
Class-wide alerts:
- Alcohol — synergistic CNS depression; combined use is the leading cause of benzodiazepine-related deaths [^36]
- Opioids — FDA black box warning for combined use (respiratory depression)
- Dependence — physiologic dependence can develop in 2-4 weeks of daily use; seizure risk with abrupt discontinuation
- Elderly — Beers Criteria lists benzodiazepines as potentially inappropriate; increased fall risk, cognitive impairment
Non-Benzodiazepine Anxiolytics
| Medication | Mechanism | Key Notes |
|---|---|---|
| Buspirone (Buspar) | 5-HT1A partial agonist | Effective for GAD; no sedation, no dependence, no abuse potential; takes 2-4 weeks for effect; avoid grapefruit (CYP3A4 substrate — grapefruit can double buspirone levels) [^37] |
| Hydroxyzine (Vistaril) | H1 antihistamine | PRN anxiety and insomnia; sedating; anticholinergic; no dependence; QTc prolongation at higher doses |
| Gabapentin (Neurontin) | Calcium channel modulator | Off-label for anxiety; dose-dependent absorption (bioavailability decreases at higher doses); increasingly recognized abuse potential; renal dosing required [^38] |
| Pregabalin (Lyrica) | Calcium channel modulator (Schedule V) | FDA-approved for GAD in Europe; linear absorption; dependence potential |
7. Clinical Safety and Monitoring
Tardive Dyskinesia (TD)
Involuntary, repetitive movements (tongue, jaw, extremities) caused by chronic dopamine receptor blockade. Can be irreversible.
- Risk factors: duration of antipsychotic exposure, older age, female sex, mood disorders
- Monitoring: AIMS (Abnormal Involuntary Movement Scale) at baseline, then q6 months for typical antipsychotics, q12 months for atypicals [^39]
- Treatment: VMAT2 inhibitors — Valbenazine (Ingrezza) and Deutetrabenazine (Austedo) are FDA-approved; reduce dopamine release into synapse
- Prevention: use lowest effective antipsychotic dose; prefer atypicals; reassess need for antipsychotic regularly
Neuroleptic Malignant Syndrome (NMS)
A life-threatening emergency. Mortality 5-20% even with treatment.
- Tetrad: high fever, lead-pipe rigidity, autonomic instability (tachycardia, labile BP, diaphoresis), altered mental status
- Labs: elevated CK (often >1000 IU/L), leukocytosis, metabolic acidosis, acute renal failure
- Management: discontinue offending agent immediately, supportive care (cooling, hydration), dantrolene and/or bromocriptine in severe cases [^40]
- Risk factors: high-potency typicals (haloperidol), rapid dose escalation, dehydration, agitation
Prescriber Alert: NMS can occur at any point during treatment, not just at initiation. Maintain a low threshold for CK levels in any patient on antipsychotics presenting with unexplained fever and rigidity.
Serotonin Syndrome
A spectrum from mild (tremor, diarrhea, restlessness) to life-threatening (hyperthermia >41°C, seizures, rhabdomyolysis).
- Most common cause: combining two serotonergic agents (e.g., SSRI + tramadol, SSRI + triptan, MAOI + any serotonergic drug)
- Hunter Criteria: clonus (spontaneous or inducible) is the most reliable clinical sign [^41]
- Management: remove offending agents, benzodiazepines for agitation, cyproheptadine (serotonin antagonist) in moderate-severe cases
- Washout periods: fluoxetine requires 5 weeks before starting an MAOI (due to long half-life of norfluoxetine); other SSRIs require 2 weeks
Insomnia Management
| Approach | Notes |
|---|---|
| CBT-I (Cognitive Behavioral Therapy for Insomnia) | First-line per ACP guidelines; more durable than medications [^42] |
| Trazodone 25-100 mg | Most commonly prescribed off-label sleep aid; orthostatic hypotension |
| Zolpidem (Ambien) | Schedule IV; short-term use only; parasomnia risk (sleep-driving, sleep-eating); lower doses in women (FDA recommendation) and elderly [^43] |
| Suvorexant (Belsomra) | Orexin receptor antagonist; less abuse potential; avoid with strong CYP3A4 inhibitors |
| Lemborexant (Dayvigo) | Dual orexin antagonist; newer option with favorable profile |
| Melatonin | OTC; most evidence at 0.5-3 mg; higher doses not more effective; useful for circadian rhythm disorders |
| Doxepin (Silenor) 3-6 mg | FDA-approved for insomnia at ultra-low doses (antihistamine effect); no anticholinergic effects at this dose |
8. Substance Use Disorder Treatment
Alcohol Use Disorder (AUD)
| Medication | Mechanism | Key Notes |
|---|---|---|
| Naltrexone (oral/Vivitrol IM) | Opioid antagonist — reduces reward from drinking | Contraindicated with concurrent opioid use (precipitates withdrawal); check LFTs; Vivitrol (monthly injection) improves adherence [^44] |
| Acamprosate (Campral) | NMDA/glutamate modulation — reduces craving | Renally eliminated (no hepatic metabolism — advantage in liver disease); must be abstinent before starting; TID dosing reduces adherence [^45] |
| Disulfiram (Antabuse) | Aldehyde dehydrogenase inhibitor — causes aversive reaction with alcohol | Requires high motivation and informed consent; reaction with alcohol includes flushing, nausea, tachycardia; hepatotoxicity risk; avoid in severe cardiac disease [^46] |
| Gabapentin | Calcium channel modulation | Off-label; evidence for reducing heavy drinking days; helpful when comorbid anxiety or insomnia |
| Topiramate | Multiple mechanisms | Off-label; evidence for reducing heavy drinking; side effects include cognitive dulling, word-finding difficulty, weight loss, kidney stones |
Prescriber Alert — Naltrexone: Patients must be opioid-free for 7-10 days before starting oral naltrexone (14 days for Vivitrol). Failure to ensure this causes precipitated withdrawal, which is a medical emergency.
Opioid Use Disorder (OUD)
| Medication | Schedule | Key Notes |
|---|---|---|
| Buprenorphine/Naloxone (Suboxone) | Schedule III | Partial mu-opioid agonist; ceiling effect on respiratory depression; patient must be in mild-moderate withdrawal before induction (COWS ≥8-12); DEA X-waiver requirement eliminated in 2023 [^47] |
| Buprenorphine (Sublocade) | Schedule III | Monthly subcutaneous injection; improves adherence; steady-state levels reduce diversion |
| Methadone | Schedule II | Full mu-opioid agonist; OTP (Opioid Treatment Program) setting only for OUD; QTc prolongation risk; many drug interactions (CYP3A4, 2B6); long and variable half-life (8-59 hours) — accumulation risk [^48] |
| Naltrexone (Vivitrol) | Not scheduled | Must be fully detoxed (7-14 days opioid-free); monthly injection; no abuse potential; blocks opioid effects |
Critical interactions with buprenorphine:
- Benzodiazepines — FDA black box warning; respiratory depression risk (though lower than full agonists)
- CYP3A4 inhibitors (ketoconazole, protease inhibitors) — increase buprenorphine levels
- Sedating medications — additive CNS depression
Tobacco Use Disorder
| Medication | Key Notes |
|---|---|
| Varenicline (Chantix) | Partial nicotinic agonist; most effective monotherapy for smoking cessation; nausea most common side effect; FDA removed black box for neuropsychiatric events in 2016 based on EAGLES trial [^49] |
| Bupropion SR (Zyban) | NDRI; lowers seizure threshold; contraindicated in eating disorders; can combine with NRT |
| Nicotine Replacement (NRT) | Patch, gum, lozenge, inhaler, nasal spray; combinations (patch + short-acting) more effective than single modality |
Prescriber Alert — Smoking cessation and psych meds: When a patient quits smoking, CYP1A2 induction stops. Medications metabolized by 1A2 — Clozapine, Olanzapine, and to a lesser extent fluvoxamine — may need dose reductions of 30-50% within days of cessation. This applies to cigarettes (combustion), not vaping or nicotine replacement [^5].
9. Critical Medication-Food-Substance Interactions Summary
| Substance | Interacts With | Effect | Action |
|---|---|---|---|
| Grapefruit juice | CYP3A4 substrates (buspirone, alprazolam, carbamazepine, lurasidone, quetiapine) | Inhibits gut CYP3A4, raising drug levels | Avoid concurrent use [^18] |
| Alcohol | All CNS-active medications | Additive sedation, respiratory depression, impaired judgment | Counsel every patient; absolute contraindication with disulfiram |
| Smoking (cigarettes) | CYP1A2 substrates (Clozapine, Olanzapine) | Induces metabolism, lowering levels | Adjust doses when smoking status changes [^5] |
| Caffeine | Lithium, CYP1A2 substrates | Increases lithium clearance; competes for 1A2 | Maintain consistent intake; sudden changes affect levels |
| High-sodium diet | Lithium | Increases lithium clearance | Consistent sodium intake; avoid drastic dietary changes |
| Low-sodium diet / dehydration | Lithium | Decreases lithium clearance → toxicity | Monitor closely in illness, heat, exercise |
| NSAIDs (OTC) | Lithium, SSRIs (bleeding) | Reduces lithium clearance; additive bleeding with SSRIs | Acetaminophen preferred; if NSAID needed, monitor lithium levels |
| St. John’s Wort | SSRIs, SNRIs, MAOIs, oral contraceptives | Serotonin syndrome risk; CYP3A4 induction | Contraindicated with serotonergic drugs [^50] |
| Tyramine-rich foods (aged cheese, cured meats, draft beer, soy sauce) | MAOIs | Hypertensive crisis | Strict dietary restriction required with MAOIs |
| Dairy / calcium / antacids | Some medications (not primary psych concern) | Can reduce absorption | Separate administration by 2 hours |
10. Quick-Reference Alerts for Prescribers
Before prescribing, always check:
- CYP2D6 status if combining bupropion, fluoxetine, or paroxetine with any 2D6 substrate
- Smoking status if prescribing Clozapine or Olanzapine — and flag the chart for future changes
- Pregnancy status/plans before valproic acid, carbamazepine, paroxetine, or lithium
- Renal function before lithium, gabapentin, pregabalin, or acamprosate
- QTc interval before haloperidol IV, citalopram >20mg, ziprasidone, or methadone
- OTC medication use — NSAIDs with lithium, antihistamines stacking anticholinergic burden
- Herbal supplements — St. John’s Wort with any serotonergic, kava with hepatotoxic agents
- HLA-B*1502 genotype in patients of Asian descent before carbamazepine (Stevens-Johnson Syndrome)
- Opioid status before naltrexone — precipitated withdrawal is a medical emergency
- Eating disorder history before bupropion — seizure risk
References
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[^5]: Zevin S, Benowitz NL. “Drug interactions with tobacco smoking.” Clin Pharmacokinet. 1999;36(6):425-438.
[^6]: Finley PR, et al. “Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction.” J Clin Psychopharmacol. 1996;16(1):68-71. See also: Handler J. “Lithium and antihypertensive medication: a potentially dangerous interaction.” J Clin Hypertens. 2009;11(12):738-742.
[^7]: Sathyanarayana Rao TS, Yeragani VK. “Hypertensive crisis and cheese.” Indian J Psychiatry. 2009;51(1):65-66.
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[^9]: Nasser A, et al. “Viloxazine extended-release for ADHD: pharmacokinetic and pharmacodynamic profile.” Expert Opin Drug Metab Toxicol. 2021;17(10):1135-1145.
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[^14]: FDA Drug Safety Communication. “Abnormal heart rhythms associated with high doses of Celexa.” August 2011.
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[^22]: GlaxoSmithKline. Wellbutrin (bupropion) prescribing information. Revised 2023.
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[^26]: Risperdal (risperidone) prescribing information. Janssen. Revised 2023.
[^27]: Zyprexa (olanzapine) prescribing information. Eli Lilly. Revised 2023.
[^28]: Stahl SM. “Mechanism of action of aripiprazole.” CNS Spectr. 2016;21(S1):11-14.
[^29]: Loebel A, et al. “Lurasidone for the treatment of bipolar depression.” J Clin Psychiatry. 2014;75(10):1047-1056.
[^30]: Clozaril (clozapine) prescribing information. Novartis. Revised 2023. See also: Clozapine REMS Program (www.clozapinerems.com).
[^31]: Cipriani A, et al. “Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis.” BMJ. 2013;346:f3646.
[^32]: Tomson T, et al. “Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug.” Lancet Neurol. 2016;15(2):210-218.
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[^35]: Greenblatt DJ, et al. “Clinical pharmacokinetics of lorazepam.” Clin Pharmacokinet. 1979;4(3):218-231.
[^36]: Jones JD, et al. “Polydrug abuse: a review of opioid and benzodiazepine combination use.” Drug Alcohol Depend. 2012;125(1-2):8-18.
[^37]: Buspirone prescribing information. Various manufacturers. See also: Mahmood I, Sahajwalla C. “Clinical pharmacokinetics and pharmacodynamics of buspirone.” Clin Pharmacokinet. 1999;36(4):277-287.
[^38]: Smith RV, et al. “Gabapentin misuse, abuse, and diversion: a systematic review.” Addiction. 2016;111(7):1160-1174.
[^39]: APA Practice Guidelines. “Tardive Dyskinesia Monitoring.” In: Practice Guideline for the Treatment of Patients with Schizophrenia. 3rd ed. 2021.
[^40]: Berman BD. “Neuroleptic malignant syndrome: a review for neurohospitalists.” Neurohospitalist. 2011;1(1):41-47.
[^41]: Dunkley EJ, et al. “The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity.” QJM. 2003;96(9):635-642.
[^42]: Qaseem A, et al. “Management of chronic insomnia disorder in adults: a clinical practice guideline from the ACP.” Ann Intern Med. 2016;165(2):125-133.
[^43]: FDA Drug Safety Communication. “Risk of next-morning impairment with zolpidem.” January 2013.
[^44]: Jonas DE, et al. “Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis.” JAMA. 2014;311(18):1889-1900.
[^45]: Mason BJ, Heyser CJ. “Acamprosate: a prototypic neuromodulator in the treatment of alcohol dependence.” CNS Neurol Disord Drug Targets. 2010;9(1):23-32.
[^46]: Wright C, Moore RD. “Disulfiram treatment of alcoholism.” Am J Med. 1990;88(6):647-655.
[^47]: SAMHSA. “Removal of DATA Waiver (X-Waiver) Requirement.” January 2023.
[^48]: Methadone prescribing information. Various manufacturers. See also: Chou R, et al. “Methadone safety: a clinical practice guideline from the APS and AAPM.” J Pain. 2014;15(4):321-337.
[^49]: Anthenelli RM, et al. “Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch (EAGLES trial).” Lancet. 2016;387(10037):2507-2520.
[^50]: Borrelli F, Izzo AA. “Herb-drug interactions with St John’s Wort: an update on clinical observations.” AAPS J. 2009;11(4):710-727.
This compendium is intended as a clinical reference for licensed prescribers. It does not replace clinical judgment, current prescribing information, or consultation with a pharmacist for complex medication regimens. Always verify interactions using an up-to-date drug interaction database (e.g., Lexicomp, Micromedex, Epocrates) before prescribing.