Switching from Oral Antipsychotics to Ziprasidone

• With aripiprazole, amisulpride, and paliperidone ER, immediate stop is possible; begin ziprasidone at an intermediate dose

• Clinical experience has shown that quetiapine, olanzapine, and asenapine should be tapered off slowly over a period of 3–4 weeks, to allow patients to readapt to the withdrawal of blocking cholinergic, histaminergic, and alpha 1 receptors

• Clozapine should always be tapered off slowly, over a period of 4 weeks or more

* Benzodiazepine or anticholinergic medication can be administered during cross-titration to help alleviate side effects such as insomnia, agitation, and/or psychosis

Suggested Reading

Komossa K, Rummel-Kluge C, Hunger H, et al. Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009;7(4):CD006627.

Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353(12):1209–23.

Nasrallah HA Jr. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 2008;13(1):27–35.

Smith LA, Cornelius V, Warnock A, Tacchi MJ, Taylor D. Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials. Bipolar Disord 2007;9(6):551–60.

Taylor D. Ziprasidone in the management of schizophrenia: the QT interval issue in context. CNS Drugs 2003;17:423–30.

ZOLPIDEM

ZOLPIDEM: THERAPEUTICS

Brands

• Ambien, Ambien CR

• Intermezzo

see index for additional brand names

Generic?

Yes

Class

• Non-benzodiazepine hypnotic; alpha 1 isoform selective agonist of GABA-A/benzodiazepine receptors

Commonly Prescribed for

(bold for FDA approved)

• Short-term treatment of insomnia (controlled-release indication is not restricted to short-term)

• As needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep and there are at least 4 hours of bedtime remaining before the planned time of wakening (Intermezzo)

How the Drug Works

• Binds selectively to a subtype of the benzodiazepine receptor, the alpha 1 isoform

• May enhance GABA inhibitory actions that provide sedative hypnotic effects more selectively than other actions of GABA

• Boosts chloride conductance through GABA-regulated channels

• Inhibitory actions in sleep centers may provide sedative hypnotic effects

• CR formulation may allow sufficient drug to persist at receptors to improve total sleep time and to prevent early morning awakenings that can be associated with the immediate release formulation of zolpidem

How Long Until It Works

• Generally takes effect in less than an hour

If It Works

• Improves quality of sleep

• Effects on total wake-time and number of nighttime awakenings may be decreased over time

If It Doesn’t Work

• If insomnia does not improve after 7–10 days, it may be a manifestation of a primary psychiatric or physical illness such as obstructive sleep apnea or restless leg syndrome, which requires independent evaluation

• Increase the dose

• Improve sleep hygiene

• Switch to another agent

Best Augmenting Combos for Partial Response or Treatment Resistance

• Generally, best to switch to another agent

• Trazodone

• Agents with antihistamine actions (e.g., diphenhydramine, tricyclic antidepressants)

Tests

• None for healthy individuals

ZOLPIDEM: SIDE EFFECTS

How Drug Causes Side Effects

• Actions at benzodiazepine receptors that carry over to the next day can cause daytime sedation, amnesia, and ataxia

• Long-term adaptations of zolpidem immediate-release not well studied, but chronic studies of zolpidem CR and other alpha 1 selective non-benzodiazepine hypnotics suggest lack of notable tolerance or dependence developing over time

Notable Side Effects

✽ Sedation

✽ Dizziness, ataxia

✽ Dose-dependent amnesia

✽ Hyperexcitability, nervousness

• Rare hallucinations

• Diarrhea, nausea

• Headache

Life-Threatening or Dangerous Side Effects

• Respiratory depression, especially when taken with other CNS depressants in overdose

• Rare angioedema

Weight Gain

• Reported but not expected

Sedation

• Many experience and/or can be significant in amount

What to Do About Side Effects

• Wait

• To avoid problems with memory, only take zolpidem or zolpidem CR if planning to have a full night’s sleep

• Lower the dose

• Switch to a shorter-acting sedative hypnotic

• Administer flumazenil if side effects are severe or life-threatening

Best Augmenting Agents for Side Effects

• Many side effects cannot be improved with an augmenting agent

ZOLPIDEM: DOSING AND USE

Usual Dosage Range

• 10 mg/day at bedtime for 7–10 days (immediate-release)

• 12.5 mg/day at bedtime (controlled-release)

Dosage Forms

• Immediate-release tablet 5 mg

• Controlled-release tablet 6.25 mg, 12.5 mg

• Sublingual tablet 1.75 mg, 3.5 mg, 5 mg, 10 mg

• Oral spray 5 mg

How to Dose

• Men: 10 mg at bedtime for 7–10 days (immediate-release); 12.5 mg at bedtime for 7–10 days (controlled-release); 3.5 mg sublingually in the middle of the night if more than 4 hours of bedtime remain (Intermezzo)

• Women: 5 mg at bedtime for 7–10 days (immediate-release); 6.25 mg at bedtime for 7–10 days (controlled-release); 1.75 mg sublingually in the middle of the night if more than 4 hours of bedtime remain (Intermezzo)

• Intermezzo formulation is administered sublingually in the middle of the night; it should be placed under the tongue and allowed to dissolve completely before swallowing

• Intermezzo formulation should not be taken more than once per night