Antidepressants

The pregnancy and postpartum periods are considered to be relatively high risk times for depressive episodes in women, particularly for those with pre-existing psychiatric illnesses. Therefore, it may be necessary to start or continue the pharmacological treatment of depression during these two timeframes. Hence, the aim of this review is to examine the effects on the fetus and infant of exposure, through the placenta and maternal milk, to the following drugs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, mirtazapine, venlafaxine, reboxetine and bupropion. The teratogenic risks, perinatal toxicity and effects on the neurobehavioural development of newborns associated with exposure through the placenta or maternal milk to these medications need to be carefully assessed before starting psychopharmacological treatment in pregnant or lactating women. In spite of the limitations of some of the studies reviewed, the older selective serotonin-reuptake inhibitors (SSRIs) [as we await further data regarding escitalopram] and venlafaxine seem to be devoid of teratogenic risks. By contrast, the data concerning possible consequences related to exposure to SSRIs via the placenta and breastmilk on neonatal adaptation and long-term neurocognitive infant's development are still controversial. Nevertheless, a number of reports have shown that an association between placental exposure to SSRIs and adverse but self-limiting effects on neonatal adaptation may exist. In addition, the information on both teratogenic and functional teratogenic risks associated with exposure to bupropion, mirtazapine and reboxetine is incomplete or absent; at present, these compounds should not be used as first-line agents in the pharmacological treatment of depression in pregnancy and breastfeeding. Untreated depression is not without its own risks since mothers affected by depression have a negative impact on the emotional development of their children and major depression, especially when complicated by a delusional component, may lead to the mother attempting suicide and infanticide. Consequently, clinicians need to help mothers weigh the risks of prenatal exposure to drugs for their babies against the potential risks of untreated depression and abrupt discontinuation of pharmacological treatment. Given these situations, we suggest that choosing to administer psychopharmacological treatment in pregnant or breastfeeding women with depression will result primarily from a careful evaluation of their psychopathological condition; currently, the degree of severity of maternal disease appears to represent the most relevant parameter to take this clinical decision.

BACKGROUND: A substantial number of women of childbearing age suffer from depression. Despite this, relatively little is known about the safety of antidepressant use during pregnancy. PURPOSE: We conducted a meta-analysis of prospective comparative cohort studies to quantify the relationship between maternal exposure to the newer antidepressants and major malformations. METHODS: We searched Medline, Embase and Reprotox from 1996 to the present for studies comparing outcomes in first trimester exposures to citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, reboxetine, venlafaxine, nefazodone, trazodone, mirtazapine and bupropion to those of non-exposed mothers. Data were combined using a random effects model; heterogeneity was tested with chi(2), and publication bias with a funnel plot and the Begg-Mazumdar statistic. RESULTS: Twenty-two studies were identified, 15 were rejected (4 reviews, 4 without comparison groups, 2 third trimester exposures, 2 retrospective database studies, 2 case reports and 1 duplicate); 7 studies (n = 1774) met inclusion criteria. Effects were not heterogeneous (chi(2) = 2.04, p = 0.92); funnel plot and test (tau = -0.24, p = 0.45) indicated no publication bias. The summary relative risk was 1.01 (95%CI: 0.57-1.80). CONCLUSIONS: As a group, the newer antidepressants are not associated with an increased risk of major malformations above the baseline of 1-3% in the population.

Bipolar Disorder Research Program, Cambridge Hospital, Cambridge, MA and Harvard Medical School, Boston, MA, USA Center on Neuroscience, Medical Progress, and Society and Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, DC, USA.

The 2002 American Psychiatric Association (APA) guidelines for the treatment of bipolar disorder recommended more conservative use of antidepressants. This change in comparison with previous APA guidelines has been criticized, especially from some groups in Europe. The Munich group in particular has published a critique of assumptions underlying the conservative recommendations of the recent APA treatment guidelines. In this paper, we re-examine the argument put forward by the Munich group, and we demonstrate that indeed, conceptually and empirically, there is a strong rationale for a cautious approach to antidepressant use in bipolar disorder, consistent with, and perhaps even more strongly than, the APA guidelines. This rationale is based on support for the following four propositions: (i) The risk of antidepressant induced mood-cycling is high, (ii) Antidepressants have not been shown to definitively prevent completed suicides and reduce mortality, whereas lithium has, (iii) Antidepressants have not been shown to be more effective than mood stabilizers in acute bipolar depression and have been shown to be less effective than mood stabilizers in preventing depressive relapse in bipolar disorder and (iv) Mood stabilizers, especially lithium and lamotrigine, have been shown to be effective in acute and prophylactic treatment of bipolar depressive episodes. We therefore draw three conclusions from this interpretation of the evidence: (i) There are significant risks of mania and long-term worsening of bipolar illness with antidepressants, (ii) Antidepressants should generally be reserved for severe cases of acute bipolar depression and not routinely used in mild to moderate cases and (iii) Antidepressants should be discontinued after recovery from the depressive episode, and maintained only in those who repeatedly relapse after antidepressant discontinuation (a minority we judge to represent only about 15-20% of bipolar depressed patients).

OBJECTIVE: To describe and compare psychiatrists' opinion on antidepressant drugs and their prescriptions to depressed patients. METHOD: Between January and September 1999 a representative sample of French psychiatrists was asked their opinion of the 15 most prescribed antidepressants, and then to describe the treatments of the current depressive episode of four depressive patients each, their changes and the reason thereof. RESULTS: A total of 232 psychiatrists and 935 patients participated. The best ranked antidepressants were clomipramine, paroxetine and amitriptyline for efficacy, tianeptine, paroxetine and citalopram for tolerability. In patients, the most often prescribed were paroxetine, fluoxetine and venlafaxine. Those least often stopped for intolerance were tianeptine (2.9%), citalopram (5.2%), venlafaxine (3.3%) and amitriptyline (5.7%) for lack of efficacy. There was no difference in stopping rates for inefficacy of tricyclics and serotonin-selective agents. CONCLUSION: The best predictors for the prescribed antidepressants were the psychiatrists' overall rankings and opinions of the tolerability of the drug.

BACKGROUND: Pharmacological treatments have been successfully used to treat Generalized Anxiety Disorder (GAD). The mainstay for the pharmacological treatment of GAD in past decades has been the use of benzodiazepine and non benzodiazepine anxiolytics. Data emerging over the last two decades have shown that antidepressants may be equally effective to anxiolytics for treating GAD. The use of antidepressants for treating GAD may be advantageous, due to the fact that GAD presents a high co morbidity ratio with major depressive disorder (62%) and dysthymia (37%). OBJECTIVES: To assess the efficacy and acceptability of antidepressants for treating generalized anxiety disorder. SEARCH STRATEGY: Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register - CCDANCTR (up to May 2002), Anxiety Neurosis (up to May 2002) and Cochrane Controlled Trials Register (CENTRAL/CCTR) (up to May 2002), MEDLINE (1966 to May 2002), LILACS (1982 to May 2002); reference searching; personal communication; conference abstracts and book chapters on the treatment of generalized anxiety disorder. SELECTION CRITERIA: Randomised controlled trials were included. Exclusion criteria were: non randomised studies; studies which included patients with generalized anxiety disorder and another Axis I co-morbidity. DATA COLLECTION AND ANALYSIS: The data from studies were extracted independently by two reviewers and relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement. MAIN RESULTS: Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating GAD. The calculated NNT for antidepressants in GAD is 5.15. Dropout rates did not differ between antidepressants. Only one study presented data on imipramine and trazodone. Imipramine was chosen as the reference drug and, therefore, data on trazodone could not be included in the meta analysis. Only one study was conducted among children and adolescents (~~Rynn 2001~~). The latter study showed very promising results of sertraline in children and adolescents with GAD, which warrants its replication in larger samples. REVIEWER'S CONCLUSIONS: The available evidence suggests that antidepressants are superior to placebo in treating GAD. There is evidence from one trial suggesting that paroxetine and imipramine have a similar efficacy and tolerability. There is also evidence from placebo-controlled trials suggesting that these drugs are well tolerated by GAD patients. Further trials of antidepressants for GAD will help to demonstrate which antidepressants should be used for which patients.