Protriptyline: side effects How Drug Causes Side Effects

✽ Anticholinergic activity for protriptyline may be more potent than for some other TCAs and may explain sedative effects, dry mouth, constipation, blurred vision, tachycardia, and hypotension

• Sedative effects and weight gain may be due to antihistamine properties

• Blockade of alpha 1 adrenergic receptors may explain dizziness, sedation, and hypotension

• Cardiac arrhythmias, especially in overdose, may be caused by blockade of ion channels

Notable Side Effects

• Blurred vision, constipation, urinary retention, increased appetite, dry mouth, nausea, diarrhea, heartburn, unusual taste in mouth, weight gain

• Fatigue, weakness, dizziness, sedation, headache, anxiety, nervousness, restlessness

• Sexual dysfunction (impotence, change in libido)

• Sweating, rash, itching

Life-Threatening or Dangerous Side Effects

• Paralytic ileus, hyperthermia (TCAs + anticholinergic agents)

• Lowered seizure threshold and rare seizures

• Orthostatic hypotension, sudden death, arrhythmias, tachycardia

• QTc prolongation

• Hepatic failure, extrapyramidal symptoms

• Increased intraocular pressure

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suidicality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

Weight Gain

• Many experience and/or can be significant in amount

• Can increase appetite and carbohydrate craving

Sedation

• Many experience and/or can be significant in amount

✽ Not as sedating as other TCAs; more likely to be activating than other TCAs

What to Do About Side Effects

• Wait

• Wait

• Wait

• Lower the dose

• Switch to an SSRI or newer antidepressant

Best Augmenting Agents for Side Effects

• Trazodone or a hypnotic for insomnia

• Benzodiazepines for agitation and anxiety

• Many side effects cannot be improved with an augmenting agent

PROTRIPTYLINE: DOSING AND USE

Usual Dosage Range

• 15–40 mg/day in 3–4 divided doses

Dosage Forms

• Tablets 5 mg, 10 mg

How to Dose

• Initial 15 mg/day in divided doses; increase morning dose as needed; maximum dose 60 mg/day

Dosing Tips

✽ Be aware that among this class of agents (tricyclic/tetracyclic antidepressants), protriptyline has uniquely low dosing (15–40 mg/day for protriptyline compared to 75–300 mg/day for most other tricyclic/tetracyclic antidepressants)

✽ Be aware that among this class of agents (tricyclic/tetracyclic antidepressants), protriptyline has uniquely frequent dosing (3–4 times a day compared to once daily for most other tricyclic/tetracyclic antidepressants)

• If intolerable anxiety, insomnia, agitation, akathisia, or activation occur either upon dosing initiation or discontinuation, consider the possibility of activated bipolar disorder, and switch to a mood stabilizer or an atypical antipsychotic

Overdose

• Death may occur; CNS depression, convulsions, cardiac dysrhythmias, severe hypotension, EKG changes, coma

Long-Term Use

• Safe

Habit Forming

• No

How to Stop

• Taper to avoid withdrawal effects

• Even with gradual dose reduction some withdrawal symptoms may appear within the first 2 weeks

• Many patients tolerate 50% dose reduction for 3 days, then another 50% reduction for 3 days, then discontinuation

• If withdrawal symptoms emerge during discontinuation, raise dose to stop symptoms and then restart withdrawal much more slowly

Pharmacokinetics

• Substrate for CYP450 2D6

• Half-life approximately 74 hours

Drug Interactions

• Tramadol increases the risk of seizures in patients taking TCAs

• Use of TCAs with anticholinergic drugs may result in paralytic ileus or hyperthermia

• Fluoxetine, paroxetine, bupropion, duloxetine, and other 2D6 inhibitors may increase TCA concentrations

• Cimetidine may increase plasma concentrations of TCAs and cause anti-cholinergic symptoms

• Phenothiazines or haloperidol may raise TCA blood concentrations

• May alter effects of antihypertensive drugs; may inhibit hypotensive effects of clonidine

• Use with sympathomimetic agents may increase sympathetic activity

• Methylphenidate may inhibit metabolism of TCAs

• Activation and agitation, especially following switching or adding antidepressants, may represent the induction of a bipolar state, especially a mixed dysphoric bipolar II condition sometimes associated with suicidal ideation, and require the addition of lithium, a mood stabilizer or an atypical antipsychotic, and/or discontinuation of protriptyline