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selective serotonin reuptake inhibitor (SSRI)

Indications: 1) depression* 2) obsessive-compulsive disorder (OCD) 3) self-injurious behavior 4) anxiety disorder * No major differences in response among SSRIs or SSRIs & atypical antidepressants. Switching for lack of response not indicated [5,14] # modestly better than placebo for treating depression, OCD, anxiety in children & adolescents [34] Contraindications: 1) children, adolescents [10] (caution) 2) NO benefit for coronary artery disease (non-indication) [15] 3) little evidence of benefit in infertile women [21] Dosage: - major depression optimal dose [30] - sertraline 120 mg QD - fluvoxamine 100 mg QD - paroxetine 20 mg QD - fluoxetine 20 mg QD - citalopram 33.3 mg QD - escitalopram 16.7 mg QD - little benefit of high doses, some evidence of harm [36] Adverse effects: 1) serotonin syndrome 2) GI bleeding* (< 2%) 3) SIADH & hyponatremia [6] 4) may inhibit growth hormone secretion & thus growth in children [7] 5) in utero effects [9,12] a) lower Apgar scores at birth b) delayed fine motor development c) common, but seldom serious [12] d) not associated with stillbirth or infant mortality [22] e) increased risk of autism in offspring of pregnant women using SSRI - relative risk < 1.61 [23]; 2.17 [31] f) exposure to SSRI in late pregnancy (>= 20 weeks of gestation) increases risk of pulmonary hypertension in newborns (RR = 2.5) [24] g) increased, but rare congenital anomalies associated with SSRI use in 1st trimester [28] h) increased likelihood of newborn admission to the NICU [33] i) discontinuation of SSRI during pregnancy associated with depression relapse, prematurity, & postpartum depression that may negatively affect a child's development [33] 6) may be associated with bone loss [16] - may increase risk of fracture in perimenopausal women [29] 7) exacerbation of parkinsonism [17] 8) REM sleep behavioral disorder [26] 9) may trigger manic attack in bipolar affective disorder, especially when not combined with lithium carbonate 10) increase in stroke risk in post-menopausal women, largely due to an increase in hemorrhagic stroke (consistent with SSRI's antiplatelet effects) (hazzard ratio 1.45) [18] - increased risk of intracranial hemorrhage in the general population [20] (1 additional case of hemorrhagic stroke per 10,000 patients/year) 11) increased risk of mortality when SSRI initiated after stroke [27] 12) sexual dysfunction, orgasm disorder - commonly associated with decreased libido & erectile dysfunction [19] - substitute with or add bupropion [38] 13) higher SSRI doses may be associated with self-harm in children & young adults [25] - no association is adults > 60 years of age [26] 14) increased risk for violence & aggressive behavior? [35] 15) withdrawal may occur if abruptly discontinued - especially with paroxetine, my result in delirium [19] 16) increased risk of falls in the elderly 36-39% in first year [37] * diminished serotonin in platelets due to diminished uptake [3,4,8,13] * patients with anxiety disorder should be counseled on potential of adverse effects & when they do occur are likely to be benign & shortlived, often a manifestation of the underlying disorder [26] Drug interactions: - tramadol, trazodone, dextromethorphan, or linezolid in combination may increase risk of serotonin syndrome [32] - triptans in combination probably do not increase risk of serotonin syndrome, although caution & vigilence is recommended [32] Laboratory: - HTR2A gene mutation - HTR2C gene mutation - HTR2A+HTR2C gene mutation Complications: - suicide children, adolescents [10], adults [11] - no association is adults > 60 years of age [26] Mechanism of action: 1) SSRI inhibit the serotonin transporter, thus the reuptake of serotonin by serotoninergic neurons 2) inhibition of serotonin uptake by platelets can impair platelet aggregation -> may decrease risk of myocardial infarction [4] 3) results in a sudden increase in serotonin, predominantly in the somatodendritic area (not axon terminals) 4) serotonin interacts with somatodendritic 5HT1A autoreceptors resulting in decreased serotonin release 5) with chronic use, somatodendritic autoreceptors desensitize resulting in an increase in serotonin release from axon terminals (2 weeks) 5) with increased release of serotonin & continued reuptake block, eventual desensitization of post synaptic receptors occurs

Interactions

drug interactions drug adverse effects (more general classes)

Related

Na+-dependent serotonin transporter; 5HT transporter; 5HTT; solute carrier family 6 member 4 (SLC6A4, HTT, SERT) serotonin & norepinephrine reuptake inhibitor (SNRI, dual-acting reuptake inhibitor) serotonin syndrome (serotonism) serotonin [5HT] receptor serotonin [5HT]-1A receptor; 5-hydroxytryptamine receptor 1A; 5-HT-1A; 5-HT1A; serotonin receptor 1A; G-21 (HTR1A, ADRB2RL1, ADRBRL1) serotonin; 5-hydroxytryptamine

Specific

citalopram (Celexa, nitalapram) fluoxetine (Prozac, Sarafem) fluvoxamine (Luvox) paroxetine (Paxil, Pexeva, Seroxat, Brisdelle) sertraline (Zoloft) sibutramine (Meridia, Reductil) vilazodone (Viibryd) zimelidine (Zimeldine, Normud, Zelmid)

General

second generation antidepressant

References

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  2. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
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