Other Warnings/Precautions

• Use with caution in patients with conditions that predispose to hypotension (dehydration, overheating)

• Dysphagia has been associated with antipsychotic use, and asenapine should be used cautiously in patients at risk for aspiration pneumonia

• Sertindole prolongs QTc interval more than some other antipsychotics

Do Not Use

• If patient is taking agents capable of significantly prolonging QTc interval (e.g., pimozide, thioridazine, selected antiarrhythmics, moxifloxacin, sparfloxacin)

• If there is a personal or family history of QTc prolongation

• If there is a history of significant cardiovascular illness, including congestive heart failure, cardiac hypertrophy, arrhythmia, bradycardia, or congential prolonged QT syndrome

• If patient has hypokalemia, hypomagnesemia, or QTc greater than 450 msec (males) or 470 msec (females)

• If patient is taking a CYP450 3A inhibitor

• If patient has severe hepatic impairment

• If patient has galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

• If there is a proven allergy to sertindole

SERTINDOLE: SPECIAL POPULATIONS

Renal Impairment

• Dose adjustment not generally necessary

Hepatic Impairment

• For mild to moderate impairment, use slower titration and lower maintenance dose

• Contraindicated in patients with severe hepatic impairment

Cardiac Impairment

• Drug should be used with caution because of risk of orthostatic hypotension

• Not recommended for patients with significant cardiovascular illness, including congestive heart failure, cardiac hypertrophy, arrhythmia, bradycardia, or congential prolonged QT syndrome

Elderly

• Use cautiously and only after thorough cardiovascular examination

• Some patients may tolerate lower doses better

• Although atypical 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 atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

Children and Adolescents

• Safety and efficacy have not been established

• Children and adolescents using sertindole may need to be monitored more often than adults

Pregnancy

• 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

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

Breast Feeding

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

✽ Recommended either to discontinue drug or bottle feed

• Infants of women who choose to breast feed while on sertindole should be monitored for possible adverse effects

SERTINDOLE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Some cases of psychosis and bipolar disorder refractory to treatment with other antipsychotics

Potential Disadvantages

• Patients requiring rapid onset of antipsychotic action without dosage titration

Primary Target Symptoms

• Positive symptoms of psychosis

• Negative symptoms of psychosis

• Cognitive symptoms

• Unstable mood (both depression and mania)

• Aggressive symptoms

Pearls

• Aimed at patients intolerant to at least one other antipsychotic and when potential benefits outweigh potential risks

• Not approved for mania, but all atypical antipsychotics approved for acute schizophrenia are generally also useful for acute bipolar mania

• Not approved for depression, but binding properties suggest potential use in treatment-resistant and bipolar depression, though probably not as a first- or second-line agent given the need to accumulate more real-world clinical experience of any actual risks of sertindole

Suggested Reading

Komossa K, Rummel-Kluge C, Hunger H, et al. Sertindole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009;2:CD006752.

Lindstrom E, Farde L, Eberhard L, Haverkamp W. QTc interval prolongation and antipsychotic drug treatments: focus on sertindole. Int J Neuropsychopharmacol 2005;8:615–29.

Spina E, Zoccali R. Sertindole: pharmacological and clinical profile and role in the treatment of schizophrenia. Expert Opin Drug Metab Toxicol 2008;4:629–38.

SERTRALINE

SERTRALINE: THERAPEUTICS

Brands

• Zoloft

see index for additional brand names

Generic?

Yes

Class

• SSRI (selective serotonin reuptake inhibitor); often classified as an antidepressant, but it is not just an antidepressant

Commonly Prescribed for

(bold for FDA approved)

• Major depressive disorder

• Premenstrual dysphoric disorder (PMDD)

• Panic disorder

• Posttraumatic stress disorder (PTSD)

• Social anxiety disorder (social phobia)

• Obsessive-compulsive disorder (OCD)

• Generalized anxiety disorder (GAD)

How the Drug Works

• Boosts neurotransmitter serotonin

• Blocks serotonin reuptake pump (serotonin transporter)

• Desensitizes serotonin receptors, especially serotonin 1A receptors

• Presumably increases serotonergic neurotransmission

✽ Sertraline also has some ability to block dopamine reuptake pump (dopamine transporter), which could increase dopamine neurotransmission and contribute to its therapeutic actions

• Sertraline also has mild antagonist actions at sigma receptors