Pregnancy

• Risk Category D [positive evidence of risk to human fetus; potential benefits may still justify its use during pregnancy]

• Not generally recommended for use during pregnancy, especially during first trimester

• Epidemiological data have shown an increased risk of cardiovascular malformations (primarily ventricular and atrial septal defects) in infants born to women who took paroxetine during the first trimester (absolute risk is small)

• Unless the benefits of paroxetine to the mother justify continuing treatment, consider discontinuing paroxetine or switching to another antidepressant

• Paroxetine use late in pregnancy may be associated with higher risk of neonatal complications, including respiratory distress

• At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

• SSRI use beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven

• Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia

• Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying

Breast Feeding

• Some drug is found in mother’s breast milk

• Trace amounts may be present in nursing children whose mothers are on paroxetine

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding

PAROXETINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients with anxiety disorders and insomnia

• Patients with mixed anxiety/depression

Potential Disadvantages

• Patients with hypersomnia

• Alzheimer/cognitive disorders

• Patients with psychomotor retardation, fatigue, and low energy

Primary Target Symptoms

• Depressed mood

• Anxiety

• Sleep disturbance, especially insomnia

• Panic attacks, avoidant behavior, re-experiencing, hyperarousal

Pearls

✽ Often a preferred treatment of anxious depression as well as major depressive disorder comorbid with anxiety disorders

✽ Withdrawal effects may be more likely than for some other SSRIs when discontinued (especially akathisia, restlessness, gastrointestinal symptoms, dizziness, tingling, dysesthesias, nausea, stomach cramps, restlessness)

• Inhibits own metabolism, so dosing is not linear

✽ Paroxetine has mild anticholinergic actions that can enhance the rapid onset of anxiolytic and hypnotic efficacy but also cause mild anticholinergic side effects

• Can cause cognitive and affective “flattening”

• May be less activating than other SSRIs

• Paroxetine is a potent CYP450 2D6 inhibitor

• SSRIs may be less effective in women over 50, especially if they are not taking estrogen

• SSRIs may be useful for hot flushes in perimenopausal women

• Some anecdotal reports suggest greater weight gain and sexual dysfunction than some other SSRIs, but the clinical significance of this is unknown

• For sexual dysfunction, can augment with bupropion, sildenafil, tadalafil, or switch to a non-SSRI such as bupropion or mirtazapine

• Some postmenopausal women’s depression will respond better to paroxetine plus estrogen augmentation than to paroxetine alone

• Nonresponse to paroxetine in elderly may require consideration of mild cognitive impairment or Alzheimer disease

• CR formulation may enhance tolerability, especially for nausea

• Can be better tolerated than some SSRIs for patients with anxiety and insomnia and can reduce these symptoms early in dosing

Suggested Reading

Bourin M, Chue P, Guillon Y. Paroxetine: a review. CNS Drug Rev 2001;7:25–47.

Gibiino S, Serretti A. Paroxetine for the treatment of depression: a critical update. Expert Opin Pharmacother 2012;13(3):421–31.

Green B. Focus on paroxetine. Curr Med Res Opin 2003;19:13–21.

Wagstaff AJ, Cheer SM, Matheson AJ, Ormrod D, Goa KL. Paroxetine: an update of its use in psychiatric disorders in adults. Drugs 2002;62:655–703.

PEROSPIRONE

PEROSPIRONE: THERAPEUTICS

Brands

• Lullan

see index for additional brand names

Generic?

No

Class

• Atypical antipsychotic (serotonin-dopamine antagonist, second generation antipsychotic)

Commonly Prescribed for

(bold for FDA approved)

• Schizophrenia (Japan)

How the Drug Works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

✽ Interactions at 5HT1A receptors may contribute to efficacy for cognitive and affective symptoms in some patients

How Long Until It Works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition and affective stabilization

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients require up to 16–20 weeks to show a good response, especially on cognitive symptoms

If It Works

• Most often reduces positive symptoms in schizophrenia but does not eliminate them

• Can improve negative symptoms, as well as aggressive, cognitive, and affective symptoms in schizophrenia

• Most schizophrenic patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third

• Perhaps 5–15% of schizophrenic patients can experience an overall improvement of greater than 50–60%, especially when receiving stable treatment for more than a year

• Such patients are considered super-responders or “awakeners” since they may be well enough to be employed, live independently, and sustain long-term relationships

• Continue treatment until reaching a plateau of improvement

• After reaching a satisfactory plateau, continue treatment for at least a year after first episode of psychosis

• For second and subsequent episodes of psychosis, treatment may need to be indefinite

• Even for first episodes of psychosis, it may be preferable to continue treatment