Mental Health: Meds and Communication

In depth

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Antidepressants in the ICU and serotonin toxicity

TCAs add sodium-channel, muscarinic, histamine and α₁ blockade to reuptake inhibition; phenelzine and tranylcypromine inhibit MAO irreversibly, so interactions last 2 weeks after the last dose (NARDIL label). Taper SSRIs and SNRIs rather than stop them: missed paroxetine or venlafaxine causes dizziness, nausea, insomnia and electric-shock sensations that can pass for delirium.

TCA overdose layers sodium-channel blockade on an anticholinergic toxidrome: coma, seizures, hypotension and a wide QRS with a tall terminal R wave in aVR. A QRS of 100 ms or more predicts seizures and 160 ms or more ventricular arrhythmias (Boehnert 1985). Give sodium bicarbonate 1–2 mEq/kg IV boluses until the QRS narrows, without pushing pH above 7.50–7.55 or sodium above 150–155 mEq/L (AHA 2023); avoid physostigmine, flumazenil and class IA or IC antiarrhythmics.

With an MAOI, meperidine can be fatal (NARDIL label) and indirect pressors such as ephedrine can trigger a crisis. Anesthesia texts allow reduced-dose direct-acting pressors; the PARNATE label restricts even epinephrine to emergencies.

The Hunter criteria (Dunkley 2003; 84% sensitive, 97% specific) need a serotonergic drug plus one of: spontaneous clonus; inducible or ocular clonus with agitation or sweating; tremor with hyperreflexia; or hypertonia, temperature above 38 °C and ocular or inducible clonus. Clonus and hyperreflexia are most obvious in the legs, and severe rigidity can mask them (Boyer 2005).

In the ICU the second drug is often not an antidepressant: linezolid and methylene blue inhibit MAO, and fentanyl, methadone, tramadol, meperidine, dextromethorphan and ondansetron are implicated. The ZYVOX label (June 2026) now asks for monitoring rather than avoidance with serotonergic drugs; in an older-adult cohort (n = 1,134) serotonin syndrome occurred in under 0.5% and antidepressants did not significantly raise the risk (Bai 2022). Methylene blue keeps a boxed warning to avoid SSRIs, SNRIs, MAOIs and opioids (PROVAYBLUE label) and makes pulse oximetry read falsely low.

Stop every serotonergic drug and sedate with benzodiazepines; physical restraint forces isometric contraction, lactic acidosis and more heat (Boyer 2005). Cyproheptadine, oral or crushed by tube, is 12 mg then 2 mg every 2 h while symptoms continue, then 8 mg every 6 h, on weak evidence (Chiew 2025). Above 39 °C with rigidity (Chiew and Isbister 2025; older texts use 41.1 °C, Boyer 2005) the heat is muscular and antipyretics do not work: sedate, paralyze with a nondepolarizing agent, intubate and cool, avoiding succinylcholine because rhabdomyolysis raises potassium.

Antipsychotics, QT and neuroleptic malignant syndrome

Antipsychotics block D₂ receptors, which can cause EPS (including airway-threatening laryngeal dystonia) and raise prolactin. High-potency typicals such as haloperidol cause the most EPS; low-potency typicals and many atypicals cause more sedation, orthostasis and anticholinergic retention, ileus and delirium. Atypicals add 5-HT₂A blockade and trade EPS for weight gain, hyperglycemia and dyslipidemia, worst with clozapine and olanzapine.

The haloperidol injection label says IV use is not approved, that IV administration and above-label doses carry more QT prolongation and torsades, that a QTc above 500 ms raises the risk, and that the ECG should be monitored when it is given IV. Droperidol’s boxed warning requires a 12-lead ECG first and bars use if the QTc exceeds 440 ms in men or 450 ms in women.

Clozapine: tobacco smoke (not nicotine) induces CYP1A2, so levels rose about 30–55% after smoking bans in two inpatient cohorts (2022–2023), and the label advises considering a lower dose. The 2025 label restarts at 40–50% of the dose after one missed day, about 25% after two, and 12.5 mg once or twice daily after longer gaps, to avoid hypotension, bradycardia and syncope. Abrupt stops can bring cholinergic rebound and psychosis, and its hypomotility can progress to ileus, ischemia and perforation, so track bowel function daily.

NMS develops over days. The 2011 international consensus (Gurrera) lists recent dopamine blockade or dopamine-agonist withdrawal, temperature above 38 °C twice, rigidity, altered mental status, CK at least 4 times the upper limit of normal, BP 25% or more above baseline or swinging by 20 mm Hg diastolic or 25 mm Hg systolic in 24 h, HR 25% and RR 50% above baseline, and a negative workup. Risk rises with high doses, rapid increases, parenteral use and switching drugs (Merck).

Stop the drug, cool, give IV fluids, and use benzodiazepines for agitation and mild rigidity. For severe cases IBCC lists dantrolene 1–2.5 mg/kg IV every 6–8 h (maximum 10 mg/kg/day), bromocriptine 2.5–5 mg by tube every 8 h (maximum 40 mg/day) and amantadine; ECT is an option if these fail. Treated mortality is about 5% at 30 days (Merck). Most patients can take an antipsychotic again (13 of 15 in Rosebush 1989), more often the longer the wait after recovery.

Lithium toxicity

Lithium is not protein-bound, distributes in 0.7–1 L/kg and is cleared by the kidney, which reabsorbs it with sodium; its half-life is 18–36 h (label). Anything that makes the kidney hold sodium raises the level: vomiting, diarrhea, low-salt diets, thiazides, NSAIDs, ACE inhibitors, ARBs and AKI.

Neurotoxicity progresses from coarse tremor, hyperreflexia and myoclonus to dysarthria, ataxia, confusion, seizures and coma; the ECG may show T-wave flattening, sinus node dysfunction, bradycardia or QT prolongation. Chronic therapy can cause nephrogenic diabetes insipidus (label), so a patient who cannot drink turns hypernatremic and more toxic, and some survivors keep permanent cerebellar deficits (SILENT).

Stop lithium and the drugs that raised it, restore volume with isotonic saline while watching sodium and urine output, and consider whole bowel irrigation for sustained-release tablets; charcoal does not bind lithium. EXTRIP (Decker 2015) recommends extracorporeal removal, preferably intermittent hemodialysis, for impaired kidney function with a level above 4.0 mEq/L, or for decreased consciousness, seizures or life-threatening dysrhythmias at any level; it suggests removal above 5.0 mEq/L, with confusion, or if reaching 1.0 mEq/L would take over 36 h. Follow serial levels for 12 h afterward, because lithium rebounds from cells; older texts dialyze lower, at about 2.5 mEq/L with symptoms or kidney injury.

Benzodiazepines and sedative withdrawal

Withdrawal resembles alcohol withdrawal, from anxiety, tremor, insomnia and tachycardia to seizures and delirium, and its timing follows the half-life, so a patient admitted on a home benzodiazepine needs it continued or replaced. Planned tapers follow the 2025 joint guideline: 5–10% every 2–4 weeks, typically no faster than 25% every 2 weeks, sometimes after switching to a longer-acting drug. Flumazenil can trigger seizures in dependent patients.

Look-alikes: interrupted intrathecal baclofen causes high fever, altered mental status, rebound spasticity and rigidity that can progress to rhabdomyolysis and death (boxed warning), mimicking sepsis, NMS or serotonin syndrome; restore baclofen. ASAM 2020 advises checking for gabapentin or carisoprodol withdrawal when alcohol withdrawal delirium lasts beyond 72 h.

Alcohol withdrawal: risk, dosing strategy and resistance

Chronic alcohol down-regulates GABA-A and up-regulates NMDA receptors, so stopping unleashes glutamate and catecholamines. ASAM 2020 endorses PAWSS for inpatients: a score of 4 or more was 93% sensitive and 99.5% specific for complicated withdrawal (Maldonado 2015). Prior seizures or DTs, acute illness, severe coronary disease, or withdrawal signs with a positive blood alcohol justify preventive dosing (ASAM 2020).

Score CIWA-Ar every 1–4 h at first, then every 4–8 h once below 10 for 24 h (ASAM 2020). Beta-blockers and clonidine lower scores without treating withdrawal, while sepsis, hypoxia and pain raise them. In delirium CIWA-Ar is invalid: use RASS or CAM-ICU and titrate IV benzodiazepine boluses to light somnolence.

Resistance has no agreed definition; studies use more than 40–50 mg IV diazepam in 1 h or 200 mg in 4 h (ASAM 2020). One 10 mg/kg IV phenobarbital dose added to a lorazepam protocol cut ED patients’ ICU admissions from 25% to 8% (Rosenson 2013, n = 102); ASAM keeps parenteral phenobarbital to closely monitored settings. Propofol suits patients already intubated; dexmedetomidine, clonidine and β-blockers treat autonomic signs only, and antipsychotics are add-ons for hallucinations.

After a withdrawal seizure give lorazepam or diazepam at once; phenytoin is not used unless there is an underlying seizure disorder (ASAM 2020). Thiamine is 100 mg IV or IM daily for 3–5 days, or 200–500 mg IV every 8 h when Wernicke signs are present or masked; replace low magnesium and phosphate.

Opioid use disorder in the hospital

Starting buprenorphine in hospital with a clinic hand-off got 72% of patients into treatment versus 12% after a 5-day detox (Liebschutz 2014, n = 139). Hospital staff may give methadone or buprenorphine to patients admitted for another condition (21 CFR 1306.07(c)), and since 2023 no special waiver is needed to prescribe buprenorphine.

Verify the home dose and last dose with the treatment program or monitoring database, and continue methadone or buprenorphine through surgery and acute illness, treating pain with multimodal analgesia, buprenorphine split every 6–8 h and, if needed, full agonists at higher doses. Extended-release naltrexone blocks opioids for about a month, so pain plans rely on regional and non-opioid options.

Buprenorphine, a high-affinity partial agonist with a ceiling on respiratory depression, displaces any full agonist still on the receptors and precipitates withdrawal if given too early. The SUBOXONE label waits for objective signs of moderate withdrawal at least 6 h after the last opioid, starts 2–4 mg, and titrates about every 2 h to 8 mg on day 1 and up to 16 mg on day 2; many protocols use a COWS of about 8–12. Because fentanyl lingers, EDs also use high-dose starts beyond the label (over 12 mg in 366 encounters with no respiratory depression, Herring 2021) or low-dose starts that overlap the full agonist.

Methadone is a full agonist with a half-life of 8–59 h whose respiratory depression peaks later and lasts longer than its effect (label), so deaths cluster during induction, after increases and when CYP3A4 inhibitors are added; programs cap the first day at 50 mg unless they document why (42 CFR 8.12). It blocks hERG potassium channels: Krantz 2009 advises an ECG before treatment, within 30 days, yearly and above 100 mg/day; at QTc 450–500 ms discuss risk and monitor more often, and above 500 ms consider a lower dose, removing other QT drugs and low potassium, or switching.

Stimulant toxicity

Cocaine blocks reuptake of norepinephrine, dopamine and serotonin and also blocks sodium channels, so severe overdose adds a wide QRS, treated with bicarbonate as for TCAs, to tachycardia, hypertension, coronary vasospasm, seizures and hyperthermia. Methamphetamine lasts many hours longer, with more psychosis, cardiomyopathy and extreme hyperthermia; MDMA adds serotonin toxicity and hyponatremia from vasopressin release and heavy water drinking.

AHA 2023 recommends sedation for severe agitation, naming benzodiazepines, antipsychotics and ketamine, and rates prolonged physical restraint without sedation as harmful; AHA 2025 prefers ice-water immersion for life-threatening hyperthermia. Check temperature, glucose, potassium, CK, creatinine, troponin and an ECG, and give fluids for rhabdomyolysis.

Cocaine chest pain gets aspirin, benzodiazepines and nitroglycerin, with phentolamine or a calcium-channel blocker for persistent hypertension. The 2014 AHA/ACC NSTE-ACS guideline advises against β-blockers in patients with signs of acute intoxication, yet a meta-analysis of 1,794 patients found no more MI or death with them (Pham 2018), so practice varies.

The agitated patient and restraint safety

Treat agitation as a symptom and look for the cause first: hypoglycemia, hypoxia, pain, a full bladder, withdrawal, intoxication or delirium (Project BETA, Wilson 2012). De-escalate before medicating: one person talks calmly and briefly, keeps a safe distance, names the feeling, sets clear limits and offers choices, including oral medication.

Ketamine is fastest but costs airway events: prehospital, 5 mg/kg IM reached adequate sedation in a median 5 versus 17 min for haloperidol 10 mg, with complications in 49% versus 5% and intubation in 39% versus 4% (Cole 2016). After any chemical restraint, monitor SpO₂ continuously, ideally with capnography, until the patient is awake.

Deaths in restraint are linked to positional asphyxia and exhaustion: struggling produces profound lactic acidosis (pH as low as 6.25 in Hick 1999), and a prone hold with weight on the back can block compensatory breathing. Keep restrained patients supine or on their side with nothing on the back, neck or face, replace restraint with sedation quickly, and check circulation, skin, breathing, fluids and toileting at the interval policy sets.

Report any death in restraint or seclusion, or within 24 h after removal, to CMS by the close of the next business day; if only soft wrist restraints were used without seclusion, record it in an internal log within 7 days (42 CFR 482.13(g)). Non-violent restraint to protect tubes is never PRN either, with renewal per hospital policy.

Suicide risk, capacity and involuntary holds

Screen with a tool such as the ASQ, which NIMH has validated in adult medical patients, and ask directly about ideation, plan, intent, means and past attempts. A positive screen leads to a 10–15 minute brief suicide safety assessment; anyone voicing current intent stays under constant observation until evaluated.

Medical and ICU rooms are not ligature-resistant, and Joint Commission NPG.08.01.01 (2026) does not require them to be; it requires 1:1 monitoring of high-risk patients, removal of self-harm objects when medically possible, checks of visitors’ items and safe transport. Search belongings per policy, remove cords, belts, bags and sharps, and weigh each necessary line or cable against its ligature risk.

Risk persists after the crisis: adding a safety plan and at least two follow-up calls to VA ED care was associated with less suicidal behavior over 6 months, 3.0% versus 5.3% (Stanley 2018). Counsel on lethal means, especially firearms, and give the 988 Lifeline.

Capacity is decision-specific and any treating clinician can assess it: the patient must communicate a choice, understand the information, appreciate how it applies to them and reason about the options (Appelbaum 2007). The bar rises with the stakes, so a patient may consent to a blood draw yet lack capacity to refuse dialysis. A patient with capacity may leave against advice; one without it, such as a delirious or intoxicated patient, can be held for emergency treatment with the reasoning documented.

Involuntary holds are state law, usually a short emergency hold (often up to 72 h) for someone dangerous to self or others or gravely disabled by mental illness. In most states a hold allows detention and evaluation, not medication over objection outside an emergency. Document the behavior and exact words behind the hold, keep observation, and never let a held patient leave unescorted.

Exam pearls

• Clonus within hours of adding linezolid, methylene blue, tramadol or fentanyl to an SSRI: serotonin syndrome.
• Lead-pipe rigidity, fever and high CK over days on an antipsychotic or metoclopramide: NMS.
• Wide QRS after a TCA or cocaine overdose: sodium bicarbonate.
• MAOI plus tyramine: occipital headache, stiff neck, severe hypertension; phentolamine. Never meperidine.
• Lithium rises with dehydration, NSAIDs, ACE inhibitors and thiazides; charcoal does not bind it.
• IV haloperidol is off-label: monitor the ECG; keep potassium and magnesium normal.
• Symptom-triggered CIWA-Ar dosing uses less drug; in delirium, titrate to RASS.
• Dexmedetomidine, clonidine and β-blockers never treat withdrawal seizures or DTs alone; nor does phenytoin.
• Start buprenorphine only in objective withdrawal; continue home buprenorphine or methadone.
• Methadone prolongs the QT: ECG before treatment, within 30 days and yearly.