Kaplan + Sadock's Synopsis of Psychiatry, 11e

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29.28 Selective Serotonin Reuptake Inhibitors

citalopram. Some persons benefit from taking their SSRI dose before going to bed, but others prefer to take it the morning. SSRI-induced insomnia can be treated with benzodiazepines, trazodone (Desyrel) (clinicians must explain the risk of pria- pism), or other sedating medicines. Significant SSRI-induced somnolence often requires switching to use of another SSRI or bupropion. Other Sleep Effects.  Many persons taking SSRIs report recalling extremely vivid dreams or nightmares. They describe sleep as “busy.” Other sleep effects of the SSRIs include brux- ism, restless legs, nocturnal myoclonus, and sweating. Emotional Blunting.  Emotional blunting is a largely over- looked but frequent side effect associated with chronic SSRI use. Patients report an inability to cry in response to emotional situations, a feeling of apathy or indifference, or a restriction in the intensity of emotional experiences. This side effect often leads to treatment discontinuation, even when the drugs provide relief from depression or anxiety. Yawning.  Close clinical observation of patients taking SSRIs reveals an increase in yawning. This side effect is not a reflection of fatigue or poor nocturnal sleep but is the result of SSRI effects on the hypothalamus. Seizures.  Seizures have been reported in 0.1 to 0.2 percent of all patients treated with SSRIs, an incidence comparable to that reported with other antidepressants and not significantly different from that with placebo. Seizures are more frequent at the highest doses of SSRIs (e.g., fluoxetine 100 mg a day or higher). Extrapyramidal Symptoms.  The SSRIs may rarely cause akathisia, dystonia, tremor, cogwheel rigidity, torticollis, opisthotonos, gait disorders, and bradykinesia. Rare cases of tardive dyskinesia have been reported. Some people with well-controlled Parkinson’s disease may experience acute worsening Anticholinergic Effects Paroxetine has mild anticholinergic activity that causes dry mouth, constipation, and sedation in a dose-dependent fashion. Nevertheless, most persons taking paroxetine do not experience cholinergic adverse effects. Other SSRIs are associated with dry mouth, but this effect is not mediated by muscarinic activity. Hematologic Adverse Effects The SSRIs can cause functional impairment of platelet aggrega- tion but not a reduction in platelet number. Easy bruising and excessive or prolonged bleeding manifest this pharmacological effect. When patients exhibit these signs, a test for bleeding time should be performed. Special monitoring is suggested when patients use SSRIs in conjunction with anticoagulants or aspirin. Concurrent use of SSRIs and nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a significantly increased risk of gastric bleeding. In cases where this combination is neces- sary, use of proton pump inhibitors should be considered. of their motor symptoms when they take SSRIs.

10 milliseconds, based on the individual correction method (QTcI). This is below the threshold for clinical concern. How- ever, it is unknown whether 80 mg is adequate to represent a high clinical exposure condition. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in SSRI treated patients with prostate cancer as reductions in androgen levels can cause QTc interval prolongation. Dextromethorphan/Quinidine (Nuedexta) is available as a treatment for pseudobulbar affect, which is defined by involun- tary, sudden, and frequent episodes of laughing or crying that are generally out of proportion or inappropriate to the situation. Quinidine that can prolong the QT interval is a potent inhibi- tor of CYP2D6. It should not be used with other medications that prolong the QT interval and are metabolized by CYP2D6. This drug should be used with caution with any medications that can prolong the QT interval and inhibit CYP3A4, particularly in patients with cardiac disease. Antepartum use of SSRIs is sometimes associated with QTc interval prolongation in exposed neonates. In a review of 52 newborns exposed to SSRIs in the immediate antepartum period and 52 matched control subjects, the mean QTc was sig- nificantly longer in the group of newborns exposed to antide- pressants as compared with control subjects. Five (10 percent) newborns exposed to SSRIs had a markedly prolonged QTc interval (greater than 460 milliseconds) compared with none of the unexposed newborns. The longest QTc interval observed among exposed newborns was 543 milliseconds. All of the drug-associated repolarization abnormalities normalized in sub- sequent electrocardiographic tracings. Headaches The incidence of headache in SSRI trials was 18 to 20 percent, only 1 percentage point higher than the placebo rate. Fluox- etine is the most likely to cause headache. On the other hand, all SSRIs are effective prophylaxis against both migraine and tension-type headaches in many persons. Anxiety.  Fluoxetine may cause anxiety, particularly in the first few weeks of treatment. However, these initial effects usually give way to an overall reduction in anxiety after a few weeks. Increased anxiety is caused considerably less frequently by paroxetine and escitalopram, which may be better choices if sedation is desired, as in mixed anxiety and depressive disorders. Insomnia and Sedation.  The major effect SSRIs exert in the area of insomnia and sedation is improved sleep resulting from treatment of depression and anxiety. However, as many as 25 percent of persons taking SSRIs note trouble sleeping, excessive somnolence, or overwhelming fatigue. Fluoxetine is the most likely to cause insomnia, for which reason it is often taken in the morning. Sertraline and fluvoxamine are about equally likely to cause insomnia as somnolence, and citalo- pram and especially paroxetine often cause somnolence. Esci- talopram is more likely to interfere with sleep than its isomer, Central Nervous System Adverse Effects