STEPTRACKERPHARMACOLOGY + PSYCHIATRY | PSYCHIATRY | HIGH-YIELD REVIEW

Mood Stabilizers, Anxiolytics & Hypnotics

Lithium has the narrowest window in psychiatry; benzodiazepines and Z-drugs share one receptor; buspirone and the newer hypnotics work differently and are safer.

FOCUS ON
Lithium: bipolar maintenance, ↓ suicide; mechanism — ↓ inositol recycling (IP₃). Narrow index, renally cleared like Na⁺ → levels ↑ with thiazides, ACEi/ARBs, NSAIDs, dehydration. Adverse: tremor, nephrogenic DI, hypothyroidism, hypercalcemia, acne, weight gain, leukocytosis, Ebstein anomaly. Toxicity: coarse tremor, ataxia, confusion, seizures → hemodialysis. Valproate, carbamazepine, lamotrigine (bipolar depression), atypical antipsychotics also stabilize mood. Benzodiazepines: ↑ frequency of GABA-A Cl⁻ opening; anxiety, panic (short term), alcohol withdrawal (chlordiazepoxide, diazepam; lorazepam/oxazepam/temazepam in liver disease), seizures, sedation. Adverse: sedation, falls, dependence, respiratory depression with alcohol/opioids → flumazenil (can cause seizures). Barbiturates: ↑ duration of opening; CYP inducers; no ceiling. Z-drugs (zolpidem, eszopiclone): BZ1; complex sleep behaviors. Buspirone: 5-HT1A partial agonist; GAD; no sedation or dependence; weeks to work. Hypnotics: ramelteon (melatonin), suvorexant (orexin), doxepin low dose, trazodone.
DRUG
MECHANISM
USE
ADVERSE · NOTES
Lithium
Inhibits inositol monophosphatase, GSK-3
Bipolar maintenance, acute mania, suicide prevention
Tremor, nephrogenic DI, hypothyroidism, hyperparathyroidism, teratogen; check levels, TSH, creatinine
Lithium toxicity
Level > 1.5 mEq/L
Coarse tremor, vomiting, ataxia, confusion, seizures
Hydration, hemodialysis (not activated charcoal)
Valproate · carbamazepine
See anticonvulsants
Acute mania, rapid cycling (valproate)
Teratogens; monitor LFTs, CBC
Lamotrigine
Na⁺ block
Bipolar depression prevention
SJS; not for acute mania
Short-acting benzodiazepines
triazolam, midazolam, alprazolam
↑ GABA-A Cl⁻ opening frequency
Insomnia, procedural sedation, panic
Rebound anxiety, dependence, withdrawal seizures
Long-acting benzodiazepines
diazepam, chlordiazepoxide, clonazepam
Same, active metabolites
Alcohol withdrawal, seizures, muscle spasm, panic (clonazepam)
Accumulate in elderly and liver disease
Lorazepam · oxazepam · temazepam
Glucuronidated only (no CYP oxidation)
Alcohol withdrawal with liver disease
Safer in cirrhosis, elderly
Flumazenil
Competitive BZ-site antagonist
Iatrogenic benzodiazepine oversedation
Seizures in dependent patients or TCA co-ingestion
Phenobarbital · pentobarbital
↑ Duration of GABA-A opening; at high dose opens directly
Seizures, induced coma, alcohol withdrawal
Respiratory depression, CYP induction; contraindicated in porphyria
Zolpidem · zaleplon · eszopiclone
BZ1 (α1) subunit of GABA-A
Insomnia
Sleepwalking, sleep-driving, next-day impairment (women)
Buspirone
5-HT1A partial agonist
Generalized anxiety disorder
No sedation, dependence or alcohol interaction; 2–4 weeks onset
Ramelteon · suvorexant · lemborexant
MT1/MT2 agonist · orexin receptor antagonists
Sleep-onset insomnia · sleep maintenance
Low abuse; suvorexant somnolence, contraindicated in narcolepsy
Hydroxyzine · propranolol
H1 antagonist · β-blocker
Acute anxiety · performance anxiety
Sedation · avoid in asthma

Mechanism — why lithium levels rise

Thiazide, ACEi, NSAID, dehydration
→
↓ Na⁺ delivery / ↓ GFR
→
↑ Proximal Na⁺ and Li⁺ reabsorption
→
Lithium toxicity

GABA-A drugs compared

DRUG
CHANNEL EFFECT
REVERSAL
Benzodiazepine
↑ Frequency
Flumazenil
Barbiturate
↑ Duration
None
Z-drug
↑ Frequency (BZ1)
Flumazenil
Alcohol
Potentiates
None

How it's tested

COMMON CONFUSIONLithium's nephrogenic DI is treated with amiloride (blocks lithium entry via ENaC) — not with desmopressin.
THE TRAPFlumazenil in an unknown overdose or a chronic benzodiazepine user can precipitate seizures — support breathing instead.
YOUR APPROACHBipolar: acute mania (antipsychotic ± lithium/valproate) vs maintenance (lithium) vs depression (lamotrigine, quetiapine, lurasidone). Anxiety: SSRI long term, benzodiazepine short term.

If you see… think…

Polyuria, polydipsia on mood stabilizer → lithium nephrogenic DI
Coarse tremor, ataxia after starting HCTZ → lithium toxicity
Ebstein anomaly → lithium in pregnancy
Anxiolytic without sedation or abuse → buspirone
Sleep-driving after a hypnotic → zolpidem
Alcohol withdrawal in cirrhosis → lorazepam, oxazepam
Seizure after flumazenil → benzodiazepine dependence
Barbiturate contraindication → acute intermittent porphyria
Orexin antagonist → suvorexant
Bipolar depression prevention without weight gain → lamotrigine