SSRI Research Abstracts

 

 

Association between selective serotonin reuptake inhibitors & upper gastrointestinal bleeding
population based case-control study.
de Abajo, FJ, Garc?a Rodr?guez LA, Montero D.
BMJ 1999;319:1106-1109 ( 23 October ).

The results of this study show that users of the antidepressants selective serotonin reuptake inhibitors (SSRI?s) have a significantly increased risk of upper gastrointestinal (GI) bleeding, compared to nonusers. The study was conducted on 1651 patients hospitalized with upper GI bleeding, and 10,000 matched controls. Use of SSRI?s was associated with a 3-fold increased risk of bleeding, compared to nonuse. The incidence of this complication was estimated at 1every 8,000 prescriptions. Combined use of SSRI?s and aspirin was associated with a 7-fold increased risk of GI hemorrhage, and combined use of SSRI?s and non-steroidal anti-inflammatory drugs resulted in a 15.6-fold increased risk. The authors emphasize that the large increase in risk of GI hemorrhage observed in their study could have important public health implications due to the frequent use of both classes of drugs in industrialized countries.

Hemorrhagic syndromes related to selective serotonin reuptake inhibitor (SSRI) antidepressants.
Seven case reports and review of the literature. French.
Nelva A, Guy C, Tardy-Poncet B, Beyens MN, Ratrema M, Benedetti C, Ollagnier M.
Rev Med Interne 2000 Feb;21(2):152-60.

The results of this study suggest that intake of the antidepressants selective serotonin reuptake inhibitors is associated with an increased risk of developing hemorrhagic syndromes. This adverse effect is under-recognized and under-reported, and may be due to a decrease in concentration of platelet serotonin, leading to platelet dysfunction.

Antidepressant Medication Use and Breast Cancer Risk.
Cotterchio M, Kreiger N, Darlington G, and Steingart A.
Am J Epidemiol 2000;151:951-57.

The results of this study indicate that women who take antidepressants are at significantly higher risk of developing breast cancer, compared to the general population. The association between antidepressant drugs and breast cancer first emerged from animal and epidemiological data. This case-control study, conducted to further test the hypothesis, found that users of selective serotonin reuptake inhibitors (SSRIs) and tryciclic antidepressants have a 7- and 2-fold increased risk of breast cancer, respectively, compared to nonusers. The finding of a large increase in risk of breast cancer in users of SSRIs may have public health implications owing to the high prevalence of use of this class of drugs.

Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry.
Kalia M, et al.
Brain Res 2000 Mar 6;858(1):92-105.

The results of this study indicate that short-term exposure to selective serotonin reuptake inhibitors (SSRIs) results in changes of rat brain cells, which resemble those induced by the recreational drug Ecstasy. SSRIs work by increasing the concentration of serotonin in the brain through inhibition of their re-uptake by brain cells. Their mode of action is similar to that of the recreational drug Ecstasy, which also increases the concentration of serotonin at the receptor site through a double action of inhibited reuptake and stimulated secretion from brain cells. While Ecstasy-induced brain damage has been well demonstrated in both animal and human studies, there are no data on the effects of SSRIs on brain cells. This study documented that, after only 4 days of intake of SSRIs, rat brain cells underwent morphological changes characterized by swelling and acquisition of a corkscrew shape, indicative of occurred damage. These findings indicate that SSRIs, the most commonly prescribed class of antidepressant drugs, cause damage in animal brain cells, after only 4 days of exposure. More studies on humans are needed, before these drugs can be considered safe.

Discontinuation symptoms and psychotropic drugs
Young, A. and Haddad P.
Lancet 2000; 355: 1181 - 1190.

This letter emphasizes that 35% to 78% of individuals who take the antidepressants selective reuptake inhibitors (SSRIs) for several months, experience, upon abrupt treatment interruption, physical and psychological symptoms such as: changes in mood, affect, appetite and sleep, dizziness, fatigue, anxiety, agitation, nausea, headache, and sensory disturbance. The symptoms are so typical that the clinical entity "SSRI discontinuation syndrome" is now widely accepted, after its existence had been negated for several years following the introduction of SSRIs on the market. Symptoms are usually mild and short-term, but occasionally can be severe and long lasting. They have often been interpreted as a sign of relapse into depression, leading to re-institution of treatment. The authors propose that all new psychotropic drugs be tested in double-blind placebo-controlled studies lasting several weeks beyond the actual drug trial, in order to properly monitor adverse reactions that may occur only upon discontinuation of treatment.

Hormonal markers of stress response following interruption of selective serotonin reuptake inhibitor treatment.
Michelson D, et al.
Psychoneuroendocrinology 2000 Feb;25(2):169-77.

The results of this study show that following abrupt interruption of treatment with selective serotonin reuptake inhibitors patients develop signs of activation of a stress response, as shown by significantly increased plasma levels of IGF-1 and heart rate.

Antidepressant discontinuation reactions.
Haddad P, Lejoyeux M, and Young A.
BMJ 1998;316:1105-1106 ( 11 April ).

This article reports on the frequency and nature of adverse reactions occurring upon discontinuation of antidepressant treatment. It explains that the existence of discontinuation reactions is often unrecognized by clinicians and that the extent of their occurrence is largely unknown because very few studies have ever addressed this issue. Discontinuation reactions usually start after few days of interruption of antidepressant treatment, and may consist of nausea, diarrhea, abdominal pain, insomnia, nightmares, headaches, lethargy, anxiety, and irritability. With selective serotonin-reuptake inhibitors, withdrawal is more commonly associated with symptoms such as dizziness, paraesthesia, numbness, and electric shock-like sensations. Results of a double blind placebo controlled study have shown that adverse reactions occur in 35% of patients after discontinuation of a 12-week treatment with the serotonin reuptake inhibitor paroxetine. Such reactions usually resolve within one day to three weeks, but occasionally they can be more severe and persist chronically, causing substantial morbidity.

Discontinuation symptoms after treatment with serotonin reuptake inhibitors
a literature review.
Zajecka J, et al.
J Clin Psychiatry 1997 Jul;58(7):291-7.

The results of this study indicate that discontinuation of selective serotonin-reuptake inhibitor therapy is associated with the development of a cluster of symptoms including dizziness, light-headedness, insomnia, fatigue, anxiety, nausea, headache, and sensory disturbance. These symptoms may last up to three weeks after interruption of treatment, and may be relieved by restarting antidepressant therapy (!).

Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine.
Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, Bagby RM.
J Clin Psychiatry 2000 Apr;61(4):276-81.

The results of this study indicate that 30%-70% of patients who take the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline experience sexual dysfunction as a side effect of treatment. Impairment in drive and/or desire occurs more frequently in men than women, while impairment in level of arousal and orgasm is experienced at similar rates by both sexes. These data indicate that the majority of patients treated with SSRIs experience sexual dysfunction. The low rates of this complication reported in previous studies were due to underreporting and was not confirmed in subsequent trials.

Sexual dysfunction induced by serotonin reuptake antidepressants.
Labbate LA, Grimes J, Hines A, Oleshansky MA, Arana GW.
J Sex Marital Ther 1998 Jan-Mar;24(1):3-12.

The results of this study show that the antidepressants selective serotonin reuptake inhibitors negatively affect sexual functios. The study was conducted on 61 individuals who took these drugs for at least two months. Both men and women experienced a significant worsening of quality of orgasm after 1 and 2 months of treatment, compared to baseline. Women reported failure to achieve an orgasm significantly more often than men, while both sexes experienced prolongation of time to orgasm induction after 1, 2, and 3 months of treatment, compared to baseline.

Incidence of sexual dysfunction in healthy volunteers on fluvoxamine therapy.
Nafziger AN, et al.
J Clin Psychiatry 1999 Mar;60(3):187-90.

The results of this study show that 35% of healthy volunteer who took the antidepressant fluvoxamine developed, after 4 weeks of treatment, sexual dysfunction.

Adverse reactions of selective serotonin reuptake inhibitors
reports from a spontaneous reporting system.
Spigset O.
Drug Saf 1999 Mar;20(3):277-87.

This study evaluated 1202 spontaneous reports on 1861 adverse reactions to selective serotonin reuptake inhibitors (SSRIs), and found that 22.4% of such reports consisted of neurological disturbances, 20% of psychiatric disorders, and 18% of gastrointestinal symptoms. The elderly were particularly susceptible to Parkinsonism, confusion, hallucinations, and hypotension, while younger patients experienced more frequently hematological, endocrine, and sexual dysfunction. Akathisia and aggression occurred more frequently in men than women.

A survey of antidepressant drug use in Parkinson's disease. Parkinson Study Group.
Richard IH, et al.
Neurology 1997 Oct;49(4):1168-70.

The results of this study indicate that approximately 26% of patients with Parkinson's disease (PD) are given antidepressant medications, which consist, in over half of the cases, of serotonin reuptake inhibitors (SSRIs). Forty-three percent of physicians of the Parkinson Study Group showed concern that use of SSRIs might induce worsening of motor function in PD patients, and 37% of physicians had at least one patient in which they believed such aggravation occurred.

Prenatal exposure to fluoxetine (Prozac) produces site-specific & age-dependent alterations in brain serotonin transporters in rat progeny
Evidence from autoradiographic studies.
Cabrera-Vera TM, Battaglia G.
J Pharmacol Exp Ther 1998 Sep;286(3):1474-81.

The results of this study show that prenatal exposure to the selective serotonin reuptake inhibitor fluoxetine (Prozac) induces changes in the density of brain serotonin transporters in rats, which are particularly evident in regions of the limbic system, such as the hypothalamus, hippocampus and amygdala. These data indicate that fluoxetine alters brain function in rats exposed to the drug while in uterus.

Pregnancy outcome following first-trimester exposure to fluoxetine.
Pastuszak A, Schick-Boschetto B, Zuber C, Feldkamp M, Pinelli M, Sihn S, et al.
JAMA 1993 May 5;269(17):2246-8.

The results of this study show that women who use the antidepressant fluoxetine (Prozac) in the first trimester of pregnancy have approximately a 2-fold increased risk of miscarriage, compared to nonusers.

Birth outcomes in pregnant women taking fluoxetine.
Chambers CD, et al.
N Engl J Med, 335(14):1010-5 1996 Oct 3.

This study evaluated pregnancy outcome of women who took the antidepressant fluoxetine (a serotonin uptake inhibitor) while expecting, and compared it to that of women who did not take the drug. In infants exposed to the drug, the incidence of three or more minor anomalies was 15.5% vs. 6.5% in controls. Infants exposed to fluoxetine during the third trimester had, compared to those exposed only during the first and second trimester, reduced birth weight and length, an almost 5-fold increased risk of premature delivery, a 2.6-fold increased risk of being admitted to special-care nurseries, and an almost 9-fold increased risk of experiencing respiratory difficulties, cyanosis on feeding, and jitteriness.

Antidepressants and suicidal risk.
Muller-Oerlinghausen B, Berghofer A.
J Clin Psychiatry 1999;60 Suppl 2:94-9; discussion 111-6.

This article emphasizes that selective serotonin reuptake inhibitors and other non-lithium antidepressants may increase the risk of suicide in certain patients by inducing akathisia (a condition characterized by restlessness and psychomotor agitation and associated with self-destructive impulses) and by liberating suppressed energies that may be used to act upon suicidal thoughts.