Pharmacokinetics

• No active metabolites

• Half-life approximately 8–15 hours

Drug Interactions

• Increased depressive effects when taken with other CNS depressants

• If temazepam is used with kava, clearance of either drug may be affected

Other Warnings/Precautions

• Insomnia may be a symptom of a primary disorder, rather than a primary disorder itself

• Some patients may exhibit abnormal thinking or behavioral changes similar to those caused by other CNS depressants (i.e., either depressant actions or disinhibiting actions)

• Some depressed patients may experience a worsening of suicidal ideation

• Use only with extreme caution in patients with impaired respiratory function or obstructive sleep apnea

• Temazepam should only be administered at bedtime

Do Not Use

• If patient is pregnant

• If patient has angle-closure glaucoma

• If there is a proven allergy to temazepam or any benzodiazepine

TEMAZEPAM: SPECIAL POPULATIONS

Renal Impairment

• Recommended dose: 7.5 mg/day

Hepatic Impairment

• Recommended dose: 7.5 mg/day

Cardiac Impairment

• Dosage adjustment may not be necessary

• Benzodiazepines have been used to treat insomnia associated with acute myocardial infarction

Elderly

• Recommended dose: 7.5 mg/day

Children and Adolescents

• Safety and efficacy have not been established

• Long-term effects of temazepam in children/adolescents are unknown

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Risk Category X [positive evidence of risk to human fetus; contraindicated for use in pregnancy]

• Infants whose mothers received a benzodiazepine late in pregnancy may experience withdrawal effects

• Neonatal flaccidity has been reported in infants whose mothers took a benzodiazepine during pregnancy

Breast Feeding

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

✽ Recommended either to discontinue drug or bottle feed

• Effects on infant have been observed and include feeding difficulties, sedation, and weight loss

TEMAZEPAM: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients with middle insomnia (nocturnal awakening)

Potential Disadvantages

• Patients with early insomnia (problems falling asleep)

Primary Target Symptoms

• Time to sleep onset

• Total sleep time

• Nighttime awakenings

Pearls

• If tolerance develops, it may result in increased anxiety during the day and/or increased wakefulness during the latter part of the night

✽ Slow gastrointestinal absorption compared to other sedative benzodiazepines, so may be more effective for nocturnal awakening than for initial insomnia unless dosed 1–2 hours prior to bedtime

✽ Notable for delayed onset of action compared to some other sedative hypnotics

• Though not systematically studied, benzodiazepines have been used effectively to treat catatonia and are the initial recommended treatment

Suggested Reading

Ashton H. Guidelines for the rational use of benzodiazepines. When and what to use. Drugs 1994;48:25–40.

Fraschini F, Stankov B. Temazepam: pharmacological profile of a benzodiazepine and new trends in its clinical application. Pharmacol Res 1993;27:97–113.

Heel RC, Brogden RN, Speight TM, Avery GS. Temazepam: a review of its pharmacological properties and therapeutic efficacy as an hypnotic. Drugs 1981;21:321–40.

McElnay JC, Jones ME, Alexander B. Temazepam (Restoril, Sandoz Pharmaceuticals). Drug Intell Clin Pharm 1982;16:650–6.

THIORIDAZINE

THIORIDAZINE: THERAPEUTICS

Brands

• Mellaril

see index for additional brand names

Generic?

Yes

Class

• Conventional antipsychotic (neuroleptic, phenothiazine, dopamine 2 antagonist)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenic patients who fail to respond to treatment with other antipsychotic drugs

How the Drug Works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

How Long Until It Works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior

If It Works

• Is a second-line treatment option

✽ Should evaluate for switching to an antipsychotic with a better risk/benefit ratio

If It Doesn’t Work

• Consider trying one of the first-line atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, amisulpride, asenapine, iloperidone, lurasidone)

• Consider trying another conventional antipsychotic

• If 2 or more antipsychotic monotherapies do not work, consider clozapine

Best Augmenting Combos for Partial Response or Treatment Resistance

✽ Augmentation of thioridazine has not been systematically studied and can be dangerous, especially with drugs that can either prolong QTc interval or raise thioridazine plasma levels

Tests

✽ Baseline EKG and serum potassium levels should be determined

✽ Periodic evaluation of EKG and serum potassium levels

• Serum magnesium levels may also need to be monitored

✽ Since conventional antipsychotics are frequently associated with weight gain, before starting treatment, weigh all patients and determine if the patient is already overweight (BMI 25.0–29.9) or obese (BMI ≥30)

• Before giving a drug that can cause weight gain to an overweight or obese patient, consider determining whether the patient already has pre-diabetes (fasting plasma glucose 100–125 mg/dL), diabetes (fasting plasma glucose >126 mg/dL), or dyslipidemia (increased total cholesterol, LDL cholesterol, and triglycerides; decreased HDL cholesterol), and treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management

✽ Monitor weight and BMI during treatment

✽ Consider monitoring fasting triglycerides monthly for several months in patients at high risk for metabolic complications and when initiating or switching antipsychotics

✽ While giving a drug to a patient who has gained >5% of initial weight, consider evaluating for the presence of pre-diabetes, diabetes, or dyslipidemia, or consider switching to a different antipsychotic

• Should check blood pressure in the elderly before starting and for the first few weeks of treatment

• Monitoring elevated prolactin levels of dubious clinical benefit

• Phenothiazines may cause false-positive phenylketonuria results

• Patients with low white blood cell count (WBC) or history of drug-induced leucopenia/neutropenia should have complete blood count (CBC) monitored frequently during the first few months and thioridazine should be discontinued at the first sign of decline of WBC in the absence of other causative factors