Other Warnings/Precautions

• Patients may be more sensitive to extreme temperatures

• Use with caution in patients with Parkinson’s disease, Lewy body dementia, or extrapyramidal symptoms with previous treatments

• Avoid undue exposure to sunlight

• Use with caution in patients with respiratory disease, Lewy body dementia, angle-closure glaucoma (including family history), alcohol withdrawal syndrome, brain damage, epilepsy, hypothyroidism, myaesthenia gravis, prostatic hypertrophy, thyrotoxicosis

• Contact with skin can cause rash

• Antiemetic effect can mask signs of other disorders or overdose

• Do not use epinephrine in event of overdose as interaction with some pressor agents may lower blood pressure

Do Not Use

• If patient is comatose

• If there is cerebral atherosclerosis

• If patient has phaeochromocytoma

• If patient has renal or liver failure, blood dyscrasias

• If patient has severe cardiac impairment

• If patient has subcortical brain damage

• If there is a proven allergy to pipothiazine

• If there is a known sensitivity to any phenothiazine

PIPOTHIAZINE: SPECIAL POPULATIONS

Renal Impairment

• Use with caution

Hepatic Impairment

• Use with caution

Cardiac Impairment

• Use with caution

Elderly

• Elderly patients do not metabolize the drug as quickly

• Dose should be reduced

• Recommended starting dose 5–10 mg

• Although conventional antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with dementia-related psychosis

• Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

Children and Adolescents

• Not recommended for use in children

Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Reports of extrapyramidal symptoms, jaundice, hyperreflexia, hyporeflexia in infants whose mothers took a phenothiazine during pregnancy

• Not recommended unless absolutely necessary

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Atypical antipsychotics may be preferable to conventional antipsychotics or anticonvulsant mood stabilizers if treatment is required during pregnancy

Breast Feeding

• Unknown if pipothiazine is secreted in human breast milk, but all psychotropics assumed to be secreted in breast milk

✽ Recommended either to discontinue drug or bottle feed

PIPOTHIAZINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Noncompliant patients

Potential Disadvantages

• Patients who need immediate onset of antipsychotic actions

Primary Target Symptoms

• Positive symptoms of psychosis

• Negative symptoms of psychosis

• Aggressive symptoms

Pearls

• Pipothiazine is a higher potency phenothiazine

• Less risk of sedation and orthostatic hypotension but greater risk of extrapyramidal symptoms than with low potency phenothiazines

✽ Only available in long-acting parenteral formulation

• Generally, patients must be stabilized on an oral antipsychotic prior to switching to parenteral long-acting pipothiazine

• Patients have very similar antipsychotic responses to any conventional antipsychotic, which is different from atypical antipsychotics where antipsychotic responses of individual patients can occasionally vary greatly from one atypical antipsychotic to another

• Patients with inadequate responses to atypical antipsychotics may benefit from a trial of augmentation with a conventional antipsychotic such as pipothiazine or from switching to a conventional antipsychotic such as pipothiazine

• However, long-term polypharmacy with a combination of a conventional antipsychotic with an atypical antipsychotic such as pipothiazine may combine their side effects without clearly augmenting the efficacy of either

• Although a frequent practice by some prescribers, adding 2 conventional antipsychotics together has little rationale and may reduce tolerability without clearly enhancing efficacy

• For treatment-resistant patients, especially those with impulsivity, aggression, violence, and self-harm, long-term polypharmacy with 2 atypical antipsychotics or with 1 atypical antipsychotic and 1 conventional antipsychotic may be useful or even necessary while closely monitoring

• In such cases, it may be beneficial to combine 1 depot antipsychotic with 1 oral antipsychotic

Suggested Reading

Leong OK, Wong KE, Tay WK, Gill RC. A comparative study of pipothiazine palmitate and fluphenazine decanoate in the maintenance of remission of schizophrenia. Singapore Med J 1989;30(5):436–40.

Quraishi S, David A. Depot pipothiazine palmitate and undecylenate for schizophrenia. Cochrane Database Syst Rev 2001;(3): CD001720.

Schmidt K. Pipothiazine palmitate: a versatile, sustained-action neuroleptic in psychiatric practice. Curr Med Res Opin 1986;10(5): 326–9.

PRAZOSIN

PRAZOSIN: THERAPEUTICS

Brands

• Minipress

see index for additional brand names

Generic?

Yes

Class

• Alpha 1 adrenergic blocker

Commonly Prescribed for

(bold for FDA approved)

• Hypertension

• Nightmares associated with PTSD

• Blood circulation disorders

• Problems urinating due to enlarged prostate

• Passing of kidney stones

How the Drug Works

• Blocks alpha 1 adrenergic receptors to reduce noradrenergic hyperactivation

• Stimulation of central noradrenergic receptors during sleep may activate traumatic memories, so blocking this activation may reduce nightmares

How Long Until It Works

• Within a few days to a few weeks

If It Works

• Reduces the severity and frequency of nightmares associated with PTSD

If It Doesn’t Work

• Increase dose

• Switch to another agent

Best Augmenting Combos for Partial Response or Treatment Resistance

• Prazosin is itself an adjunct agent for the treatment of nightmares associated with PTSD

Tests

• None for healthy individuals.

• False positive results may occur in screening tests for pheochromocytoma in patients who are being treated with prazosin; if an elevated urinary VMA is found, prazosin should be discontinued and the patient retested after a month.

PRAZOSIN: SIDE EFFECTS

How Drug Causes Side Effects

• Excessive blockade of alpha 1 peripheral noradrenergic receptors

Notable Side Effects

• Dizziness, lightheadedness, headache, fatigue, blurred vision

• Nausea

Life-Threatening or Dangerous Side Effects

• Syncope with sudden loss of consciousness

Weight Gain

• Reported but not expected

Sedation

• Occurs in significant minority

What to Do About Side Effects

• Lower the dose

• Wait

• Wait

• Wait

• In a few weeks, switch to another agent

Best Augmenting Agents for Side Effects

• Often best to try another treatment prior to resorting to augmentation strategies to treat side effects

PRAZOSIN: DOSING AND USE

Usual Dosage Range

• 1–16 mg/day, generally in divided doses

Dosage Forms

• Capsule 1 mg, 2 mg, 5 mg

How to Dose

• Formal dosing recommendations for treating nightmares have not been established

• Initial 1 mg at bedtime; increase dose (divided) until the nightmares resolve or an intolerable side effect occurs

Dosing Tips

• Dosing may be extremely individualized, with as little as 2 mg/day helpful for some patients and as much as 40 mg/day necessary for other patients

• Therapeutic dose does not correlate with blood levels

• Divided dosing may be preferable; in particular, giving a smaller dose during the day may be beneficial if the patient has persistent hyperarousal and re-experiencing symptoms during the day

• Risk of syncope can be decreased by limiting the initial dose to 1 mg and using slow dose titration

Overdose

• No fatalities have been reported; sedation, depressive reflexes, hypotension

Long-Term Use

• Has not been evaluated in controlled studies

• Nightmares may return if prazosin is stopped

Habit Forming

• No

How to Stop

• Taper to avoid hypertension

Pharmacokinetics

• Elimination half-life 2–3 hours

Drug Interactions

• Concomitant use with a phosphodiesterase-5 inhibitor (PDE-5) can have additive effects on blood pressure, potentially leading to hypotension; thus, a PDE-5 inhibitor should be initiated at the lowest possible dose

• Concomitant use with a beta blocker (e.g., propranolol) can have additive effects on blood pressure

• Concomitant use with other alpha 1 blockers, which include many psychotropic agents, can have additive effects leading to hypotension