All available antidepressants cause side-effects in a fair number of patients.  Patients having to discontinue any single antidepressant due to side-effects range from 10% to 26%, depending on the medication.  Some side-effects will fade with time, some can be countered by a medication for side-effects, and often an alternative medication has to be tried.

The SSRI family of antidepressants has its share of side-effects.  Articles on some of these are listed below.

Birth Defects: SSRIs Linked to Increase in Birth Defects: SSRI use in the first three months of pregnancy is linked to a 40% increased risk of cleft palate - but the results are preliminary. Cardiac defects appeared to be 60% more likely when the women used SSRIs.  Pulse magazine. In a study of 1,054 women who took SSRIs during pregnancy, scientists also found that use of the drugs late in pregnacy was associated with a 40% increased risk of premature birth. And a second study of 377 cases of persistent pulmonary hypertension in babies found SSRI use late in pregnancy was linked a 5.5-fold increased risk. Previous studies have shown differing results, some showing no difference in birth defects in women taking antidepressants to the average population rate. Henrik Toft Sorensen, et al. International Society for Pharmacoepidemiology conference. BBC News 9/1/05

Bleeding: SSRIs Increase General Bleeding Risk: Serotonin plays a role in platelet aggregation. In a nested case-control study of a group of more than 64 000 patients using antidepressants for the first time, researchers identified 196 cases of abnormal bleeding, which included uterine bleeding, bleeding in the upper gastrointestinal tract, cerebral bleeding, hematuria, nose bleeds, hemoptosis, hemarthrosis, hematoma, and excessive bleeding after surgery. The risk of admission to hospital from one of these increased with the use of inhibitors that provided intermediate (OR 1.9) and high levels of serotonin reuptake inhibition (OR 2.6). Utrecht, the Netherlands. Arch Intern Med 2004;164:2367-70.

Bruxism: SSRI Bruxism Treated with Buspirone: 4 cases of patients on sertraline 100-150 mg/d reports in first few weeks few weeks of treatment developing a tight and clenching jaw. Two also had severe headaches. Buspirone (Buspar) was helpful. Bostwick, Mayo, J Clin Psych 99;60:857; similar reports with others SSRIs also responding to buspirone which doesn’t help if the bruxism is due to neuroleptics.

GI Bleed: SSRIs Increase Risk: 26,000 Danes on antidepressants. Bleeds with SSRI 3.6 times general population. With NSAID, 12-fold increase risk of hospitalization. With balanced TCAs (imipramine, etc), risk 2.3 times, but no increase with other antidepressants. Serotonin contributes to hemostasis. Rates similar with all SSRIs. Dalton, Arch Int Med ’03;163:59-64

Hyponatremia: SSRI Hyponatremia (Low Sodium) and SIADH: The author reports a well proven case of sertraline hyponatremia with sodium as low as 122 mmol/L with somnolent, unresponsive, cachectic, and Babinski reflexes. Other cases have been reported with fluoxetine. Levsky, NWU, J Amer Geriatrics Society 98;46:1582; Five cases with citalopram, 4 female and all over 65. Ann Pharmacoth 02;36:1558

Hyponatremia: SSRI Hyponatremia SIADH Common in Elderly on Paroxetine: In a prospective study of 15 elderly started on paroxetine, researcher found hyponatremia in 6 by second week without appropriate suppression of ADH causing low serum osmolality. Paroxetine-induced hyponatremia in the elderly due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Fabian TJ, Amico JA, Kroboth PD, Mulsant BH, Reynolds CF 3rd, Pollock BG. J Geriatr Psychiatry Neurol 2003 Sep;16(3):160-4

Hyponatremia: SSRI Cause Hyponatremia: 35 articles have reported. Median onset 13 days (3-120) and esp >65yo.

Hyponatremia: SSRI Hyponatremia Common in Elderly: 83% of those affected were over age 64 in the 736 published cases. Of 53 elderly on SSRIs, 25% had hyponatremia which developed only 2 weeks after starting on average. Usually mild, asymptomatic and transient. Can cause confusion, weakness, lethargy, drowsiness, cognitive and neurologic and depressive symptoms including seizures, falls, and death. Usually resolves in 2 weeks with stopping the SSRI. Kirby, Int J Ger Psyc 01;16:484; Liu, Can Med Assoc J 96;155:519; Strachan, Aust NZ J Psyc 98;32:295.

Newborn Withdrawal: Antidepressants Can Cause Withdrawal Symptoms in Some Newborns: Antidepressants can cause a withdrawal syndrome in newborns.  Symptoms include convulsions, irritability, abnormal crying and tremor. As of November 2003, a total of 93 cases of SSRI antidepressant use have been reported associated with either neonatal convulsions or withdrawal syndrome.  Of these, 64 were associated with Paxil (paroxetine), 14 with Prozac (fluoxetine), nine with Zoloft (sertraline) and seven with Celexa (citalopram). Emilio Sanz, University of La Laguna, Spain, Lancet 2/5/2005. Ed: Unfortunately, these are reports from the entire world and do not reflect how common the problem is.  It does appear that the short-acting SSRI antidepressant paroxetine (Paxil) is the worst offender.  It also causes more severe withdrawal symptoms in adults who discontinue its usage.  Very likely, other antidepressants with severe withdrawal effects, such as venlafaxine (Effexor), cause the same problem.  Paroxetine and venlafaxine should probably be avoided in pregnant women and the dosage of any necessary antidepressant should be kept to a minimum.

Neonatal Withdrawal: five cases of neonatal withdrawal syndrome after third trimester in utero SSRI exposure. In three cases the mother used paroxetine in doses from 10 to 40 mg, one mother used citalopram 30 mg, and one mother fluoxetine 20 mg. Withdrawal symptoms occurred within few days after birth and lasted up to one month after birth. Four of the infants needed treatment with chlorpromazine. Symptoms were irritability, constant crying, shivering, increased tonus, eating and sleeping difficulties and convulsions. U Oslo. Acta Paediatr 2001 Mar;90(3):288-91

Sexual Disinhibition: 5 cases from Germany of very uncharacteristic sexual behavior after starting or just after stopping SSRI: excess preoccupation with porn, increased sex drive and preoccupation with multiple encounters, elated mood with promiscuity and unsafe sex, homo prostitute encounters. All symptoms stopped with discontinuation. Greil, J Aff Disorders 01;62:225

Sex Dysfunction: Between 30% and 60% of SSRI-treated patients may experience some form of treatment-induced sexual dysfunction. Bupropion and nefazodone appear to be much less likely to cause sexual dysfunction (less than 10% of patients). Mirtazapine also appears to be associated with a low rate of sexual adverse effects. Ann Pharmacother 2002 Oct;36(10):1577-89

Sex Dysfunction: Ginkgo No Benefit for SSRI Sex Dysfunction: 22 patients given in open trial. At one month, only 3 reported at least partial improvement. Am J Psychiatry 5/00. An earlier study found benefit. Cohen J Sex Martial Ther 98;24:139

Sex Dysfunction: Buspirone Helped SSRI Sex Dysfunction: In a 47- patient DB PC 4 weeks study of 20-60 mg/day buspirone in patients having sexual difficulties due to an SSRI, 65% on buspirone vs. 30% on placebo reported benefit. Benefit was noted in first week and didn’t improve further after the first week. It was more beneficial in women. Effect of buspirone on sexual dysfunction in depressed patients treated with selective serotonin reuptake inhibitors. Landen M, Eriksson E, Agren H, Fahlen T. J Clin Psychopharmacol 1999 Jun;19(3):268-71

Sex Dysfunction: Ropinirole (Requip) Used for Anti-Depressant Sexual Dysfunction: An anti-Parkinsonian medication which is a dopamine agonist with specificity at the D2 and D3 doopamine receptor sites. 10 male and 3 female outpatients experiencing antidepressant sexual dysfunction received 0.25mg/d then were increased gradually to 2-4 mg/d. After 4-8 weeks, 7 of 13 were much improved and one dropped out due to abdominal pain. Worthington J III, et al: Ropinirole for antidepressant-induced sexual dysfunction. Internat Clin Psychopharm 2002;27:307-310, MGH. In double-blind Parkinson's studies, 24% stop Ropinirole due to side-effects vs. 13% with placebo. Most common side-effects were nausea, dizziness, sleepiness, headache, vomiting, fainting, and fatigue. 

Sex Dysfunction: Sildenafil (Viagra) Helped: In a 6-week PC DB study of 90 men with Major Depression treated with an SSRI for 12 weeks or more and who had recovered from depression yet had sexual dysfunction were told to take a pill at least twice a week for sexual activity. Viagra patients averaged 5.3 times per two week period or 11 times per month ($110). 54% of Viagra vs. 4% placebo patients reported much improved. Univ New Mexico funded by Pfizer. Nurnberg H, et al: Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial. JAMA 2003;289:56-64.

Withdrawal From SSRIs: Paroxetine Highest, Then Sertraline, Least Fluoxetine: Controlled study abrupt d/c 107 patients successfully treated for depression. Dizziness most common withdrawal symptom 57% parox & 42% sertraline. Paroxetine also nausea, weird dreams, fatigue, irritable, difficulty concentrating, aches, tense, chills, insomnia, agitation, diarrhea. Sertraline did have nausea and weird dreams. HAM-D increased with paroxetine. Brit J Psychiatry 00;176:363, Michelson. Withdrawal symptoms reported in less than 5% fluoxetine and as many as 86% fluvoxamine although fluvoxamine is usually less likely than shorter acting SSRIs, the latter was in a study of panic disorder patients. Symptoms can include hypomania, increased depression, agressiveness, and suicidality. Withdrawal symptoms can last up to 3 weeks and are sometimes helped by restarting the drug and tapering more gradually or using another anti-depressant with a similar profile. Zajecka J, et al: Discontinuation symptoms after treatment with serotonin reuptake inhibitors: a literature review. J Clin Psyc 97;58:291-7.

Withdrawal: Paroxetine Withdrawal Marked But Not Fluoxetine, Citalopram or Sertraline: 85 pt in DB studies had DB 4-7 substitution of placebo for med. Only paroxetine patients suffered noticeable withdrawal effects: cognitive failures (P = 0.007), poorer quality of sleep (P = 0.016), and an increase in depressive symptoms, as rated both subjectively, using the Zung scale (P = 0.006) and by the clinician, using the Montgomery-Asberg Depression Rating Scale (P = 0.0003) and Clinical Global Impression (P = 0.0003). These cleared on restarting med. U Surrey. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance. Hindmarch I, Kimber S, Cockle SM. Int Clin Psychopharmacol 2000 Nov;15(6):305-18