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Name: Doxepin Hydrochloride

Pregnancy Category C

Drug classes

  • TCA (tertiary amine)
  • Antianxiety drug

Mechanism of actions

Mechanism of action unknown; TCAs inhibit the reuptake of the neurotransmitters norepinephrine and serotonin, leading to an increase in their effects; anticholinergic at CNS and peripheral receptors; sedative.


  • Relief of symptoms of depression (endogenous depression most responsive); sedative effects of tertiary amine TCAs may be helpful in patients whose depression is associated with anxiety and sleep disturbance
  • Treatment of depression in patients with manic-depressive illness
  • Antianxiety agent


  • Contraindicated in the presence of hypersensitivity to any tricyclic drug; concomitant therapy with an MAO inhibitor; recent MI; myelography within previous 24 h or scheduled within 48 h; lactation.
  • Use caution in the presence of electroshock therapy; preexisting cardiovascular disorders (severe coronary heart disease, progressive heart failure, angina pectoris, paroxysmal tachycardia); angle-closure glaucoma, increased intraocular pressure, urinary retention, ureteral or urethral spasm; seizure disorders; hyperthyroidism; impaired hepatic, renal function; psychiatric patients (schizophrenic or paranoid patients may exhibit a worsening of psychosis with TCA therapy); manic-depressive patients; elective surgery (TCAs should be discontinued as long as possible before surgery).

Adverse effects

  • CNS: Sedation and anticholinergic (atropine-like) effects; confusion (especially in elderly), disturbed concentration, hallucinations, disorientation, decreased memory, feelings of unreality, delusions, anxiety, nervousness, restlessness, agitation, panic, insomnia, nightmares, hypomania, mania, exacerbation of psychosis, drowsiness, weakness, fatigue, headache, numbness, tingling, paresthesias of extremities, incoordination, motor hyperactivity, akathisia, ataxia, tremors, peripheral neuropathy, extrapyramidal symptoms, seizures, speech blockage, dysarthria, tinnitus, altered EEG
  • GI: Dry mouth, constipation, paralytic ileus, nausea, vomiting, anorexia, epigastric distress, diarrhea, flatulence, dysphagia, peculiar taste, increased salivation, stomatitis, glossitis, parotid swelling, abdominal cramps, black tongue, hepatitis, jaundice (rare); elevated transaminase, altered alkaline phosphatase
  • CV: Orthostatic hypotension, hypertension, syncope, tachycardia, palpitations, MI, arrhythmias, heart block, precipitation of CHF, stroke
  • Hematologic: Bone marrow depression, including agranulocytosis; eosinophila, purpura, thrombocytopenia, leukopenia
  • GU: Urinary retention, delayed micturition, dilation of the urinary tract, gynecomastia, testicular swelling in men; breast enlargement, menstrual irregularity and galactorrhea in women; increased or decreased libido; impotence
  • Endocrine: Elevated or depressed blood sugar; elevated prolactin levels; inappropriate ADH secretion
  • Hypersensitivity: Skin rash, pruritus, vasculitis, petechiae, photosensitization, edema (generalized or of face and tongue), drug fever
  • Withdrawal: Symptoms on abrupt discontinuation of prolonged therapy: nausea, headache, vertigo, nightmares, malaise
  • Other: Nasal congestion, excessive appetite, weight gain or loss; sweating (paradoxical effect in a drug with prominent anticholinergic effects), alopecia, lacrimation, hyperthermia, flushing, chills

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