Adverse Effects Of Antidepressants Research Articles

Can antidepressant use be associated with emotional blunting in a subset of patients with depression? A scoping review of available literature.

Despite frequent recognition of emotional blunting in the published literature, either as a primary symptom of depression or as an adverse effect of antidepressants, there is no systematic synthesis on this topic to our knowledge. We undertook this scoping review to assess the prevalence, clinical features, implicated causes and management of emotional blunting, outlining the phenomenological and clinical gaps in research. A systematic search was done until March 15, 2022, to include all original studies (i.e., interventional trials, cohort & cross-sectional studies, case reports, and case series). All reviewed data were delineated to answer pertinent clinical, phenomenological, and management questions related to the phenomenon of emotional blunting. A total of 25 original studies were included in our scoping review. Emotional blunting was described as a persistent diminution in both positive and negative feelings in depressed patients, who could subjectively differentiate it from their acute symptoms. However, the literature lacked the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants. Common clinical strategies to manage antidepressant-induced emotional blunting included dose reduction or switching to a different antidepressant. Emotional blunting was a significant patient-reported concern with antidepressants. Future research should clarify phenomenological and neurobiological constructs underlying emotional blunting to improve diagnostic and management skills.

Pairing with Enriched Sound Exposure Restores Auditory Processing Degraded by an Antidepressant.

Antidepressants, while effective in treating depression and anxiety disorders, also induce deficits in sensory (particularly auditory) processing, which in turn may exacerbate psychiatric symptoms. How antidepressants cause auditory signature deficits remains largely unknown. Here, we found that fluoxetine-treated adult female rats were significantly less accurate when performing a tone-frequency discrimination task compared with age-matched control rats. Their cortical neurons also responded less selectively to sound frequencies. The degraded behavioral and cortical processing was accompanied by decreased cortical perineuronal nets, particularly those wrapped around parvalbumin-expressing inhibitory interneurons. Furthermore, fluoxetine induced critical period-like plasticity in their already mature auditory cortices; therefore, a brief rearing of these drug-treated rats under an enriched acoustic environment renormalized auditory processing degraded by fluoxetine. The altered cortical expression of perineuronal nets was also reversed as a result of enriched sound exposure. These findings suggest that the adverse effects of antidepressants on auditory processing, possibly because of a reduction in intracortical inhibition, can be substantially alleviated by simply pairing drug treatment with passive, enriched sound exposure. They have important implications for understanding the neurobiological basis of antidepressant effects on hearing and for designing novel pharmacological treatment strategies for psychiatric disorders.SIGNIFICANCE STATEMENT Clinical experience suggests that antidepressants adversely affect sensory (particularly auditory) processing, which can exacerbate patients' psychiatric symptoms. Here, we show that the antidepressant fluoxetine reduces cortical inhibition in adult rats, leading to degraded behavioral and cortical spectral processing of sound. Importantly, fluoxetine induces a critical period-like state of plasticity in the mature cortex; therefore, a brief rearing under an enriched acoustic environment is sufficient to reverse the changes in auditory processing caused by the administration of fluoxetine. These results provide a putative neurobiological basis for the effects of antidepressants on hearing and indicate that antidepressant treatment combined with enriched sensory experiences could optimize clinical outcomes.

Emotional blunting with bupropion and serotonin reuptake inhibitors in three randomized controlled trials for acute major depressive disorder

BackgroundEmotional blunting is theorized to be an adverse effect of antidepressants, particularly serotonin reuptake inhibitors, but this has not been firmly established. Another possibility is that emotional blunting represents a residual depressive symptom. MethodsWe analyzed data from adult outpatients with acute major depressive disorder who participated in three 8-week randomized controlled trials. Trials 1 and 2 were pooled (venlafaxine, n = 378; bupropion, n = 389; placebo, n = 383) and Trial 3 (escitalopram, n = 254; bupropion, n = 260) was analyzed separately. Emotional blunting was measured with the “inability to feel” item from the Montgomery-Åsberg Depression Rating Scale. ResultsEmotional responsiveness improved, on average, in all treatment groups. Only a minority of participants (≤6 %) experienced more emotional blunting post-treatment, compared to baseline, with no significant differences between treatment groups, although roughly 20–25 % continued to report an inability to feel normal emotions at the final assessment. In Trials 1 and 2, emotional blunting was associated with poorer outcomes in terms of depressive symptoms, suicidal ideation, and sexual function, but these correlations were nearly identical in the placebo group. LimitationsThe trials were short and cannot speak to the possibility of emotional blunting from long-term treatment. Emotional blunting was measured with a single item. ConclusionsThe study medications did not significantly decrease emotional responsiveness, and there was no evidence that emotional blunting mediated treatment response. In acute treatment, emotional blunting may be better conceptualized as a residual symptom than as an adverse drug effect.

Pharmacotherapy for late-life depression

Background: Late-life depression (LLD) is one of the most common psychiatric disorders. However, LLD is often undetected or inadequately treated by clinicians. This review summarizes the recent research on pharmacotherapy for LLD, updates information on monotherapy using recommended antidepressants, and discusses the clinical features and diagnostic criteria for LLD.Current Concepts: The diagnostic criteria for depression in both elderly and young adults are identical. Clinical features of the elderly with depression more likely include more comorbid medical conditions and cognitive impairment than those of young adults. Depression in the elderly tends to have a more chronic course with frequent recurrences or relapses.Discussion and Conclusion: The current pharmacological treatment guidelines for LLD recommend the use of selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor, bupropion, mirtazapine, and vortioxetine as first-line medications. SSRIs, among them, are recommended first because they present fewer serious adverse effects and more clinical evidence than those of other antidepressants. Before starting antidepressant treatment for LLD, clinicians should consider patients’ comorbid medical conditions, drug interactions, possible adverse effects of antidepressants, and polypharmacy. The starting dose of antidepressants for elderly patients should be half of that prescribed for young adults to minimize the adverse effects; however, most elderly patients need the same antidepressant doses as that prescribed for young patients. After remission, a 1-year maintenance treatment is required to prevent recurrence or relapse of LLD.

L’utilisation des antidépresseurs dans l’épisode dépressif caractérisé unipolaire du sujet âgé

ObjectiveTo study the ageing-related pharmacological modifications about major depressive episodes in the elderly and their impact on the efficiency and tolerability of antidepressants. MethodsResearch through Pubmed and the Cochrane Database of Systematic Reviews, using the following keywords “antidepressant” ; “treatment”; “late life depression”; “elderly”; up until July 2021. ResultsAntidepressants were found to be more efficient than a placebo in the elderly's response to and remission from major depressive episodes. Some depressive episode subtypes seem to be less responsive to antidepressants, such as depressive episodes of vascular origin, for which treating cardiovascular risk factors by statins, angiotensin receptor blockers or calcium channel blockers seems relevant. Two other depressive episode subtypes were highlighted : post-stroke depressive episodes and those induced by major neurocognitive disorders. Antidepressants showed an efficient response in the first case but not in the second. Even though antidepressants are known to stimulate cognitive performances in animals, as yet there is not sufficient evidence to prove they indeed improve cognitive functions, or reduce the risk of developing a neurocognitive disorder, or decelerate the cognitive decline in major neurocognitive disorders in humans. Ageing creates pharmacodynamical changes that increase older people's vulnerability to the side effects of antidepressants. Moreover, age-related pharmacokinetic modifications can also change every step in a drug's transformation process in the body, which leads to a high probability of having adverse effects. Since most antidepressants are eliminated using the P450 cytochrome system, their dosage must be adapted to changes of the P450 system. Somatic comorbidities can, in themselves, influence the pharmacokinetics of antidepressants. Many antidepressants interact with the P450 cytochrome and the P-GP protein, which puts them at a high risk of drug interactions. There is no proven efficiency difference between antidepressant classes. Some antidepressant adverse effects can be of particular importance in the elderly, like the risk of bleeding, cardiovascular episodes, hyponatremia, falling and fractures, anticholinergic effects, extrapyramidal syndrome, epilepsy, liver disease and death. Selective serotonin reuptake inhibitors have an indication as the first line of treatment, avoiding paroxetine and fluoxetine. Serotonin and norepinephrine re-uptake inhibitors are relevant if the patient presents psychomotor retardation or pain, while keeping in mind to check blood pressure. Tricyclics and monoamine oxidase inhibitors should be avoided because of their anticholinergic effects. Bupropion can be prescribed if the patient has extreme fatigue. Mirtazapine is useful when the patient presents sleep or appetite disturbance. Several molecules can be used in the case of drug-resistant depression, such as associating aripiprazole with small-dosage antidepressants, or electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation (rTMS). Ketamine and psychostimulants seem to have antidepressant effects, but complementary studies are needed to conclude. ConclusionsUnipolar major depressive episodes in the elderly are frequent and their medicinal treatment has specific features. Knowing the specificities of antidepressant use in the elderly allows to optimize its efficiency and to limit the risk of inappropriate prescription leading to harmful adverse effects.

Ketamine; A better anti-depressant? An animal study evaluating the efficacy of citalopram, ketamine and their combination in animal models of depression

Background: Despite the availability of vast group of drugs, treatment of depression still remains unsatisfactory, largely due to differential efficacy of antidepressants at adequate doses resulting in treatment refractive depression. In addition, serious adverse effects of anti-depressants also lead to early withdrawal from treatment. One more important concern is the therapeutic lag of nearly 3-4 weeks, before some appreciable clinical effect. Therefore, newer agents with good safety profile, rapid onset of action and with substantial benefits in treating patients who are either refractory or resistant to conventional therapy, need to be explored. Methods: 8 groups of 6 mice each were evaluated for anti-depressant effect in Tail Suspension Test and Forced Swim Test. Treatment used was normal saline (control), citalopram, ketamine and combination of ketamine with citalopram. Results: Citalopram decreased the immobility time in both models but it was not significant in FST. Significant decrease in immobility time was observed in ketamine treated mice in both models. Ketamine and citalopram combination also decreased the immobility time significantly. Conclusion: Ketamine have an antidepressant activity of its own, as shown in both TST & FST models. Additionally, it also potentiated the antidepressant effect of citalopram, which could be attributed to possible involvement of NMDA receptors and its interaction with the monoaminergic system.

Pharmacogenetics and therapeutic drug monitoring of fluoxetine in a real-world setting: A PK/PD analysis of the influence of (non-)genetic factors.

This work presents the GnG-PK/PD-AD study-a pharmacokinetics/pharmacodynamics (PK/PD) analysis of the impact of genetic and nongenetic factors on the treatment with the antidepressant fluoxetine (FLU)-with a focus on potential biomarkers. Seventy-nine depressed patients treated with FLU were recruited and clinically characterized in the scope of the study. Clinical outcomes, including remission and antidepressant adverse effects were assessed by means of the Hamilton Depression Rating Scale and the Antidepressant Side-Effect Checklist, respectively. Patients were submitted to therapeutic drug monitoring of FLU and norfluoxetine and genotyping of the CYP2C9, CYP2C19, CYP2D6, and ABCB1 genes. A multivariate analysis was used to evaluate the impact of genetic and nongenetic factors on the drug plasma concentrations and clinical outcomes and to identify potential biomarkers. Genetically determined CYP2D6 activity was found to be a predictor of FLU and norfluoxetine concentrations (p < .05). In turn, genetic and nongenetic factors related to CYP2D6 and P-glycoprotein were found as potential biomarkers of the clinical outcomes of FLU (p < .05). Specifically, the potential of the CYP2D6 to be inhibited by drug-induced phenoconversion was associated with a higher severity of depression (p < .05). Moreover, ABCB1 TTT-haplotype was favorable to better clinical outcomes with FLU (higher likelihood of remission and lower severity of adverse effects; p < .05). The potential of the P-glycoprotein to be inhibited by drug-induced phenoconversion was also related to a worse tolerability profile (higher severity and number of adverse effects; p < .05). Lastly, the presence of nervous system comorbidities was associated with a higher severity of adverse effects and aging and the female gender with a higher severity of depression and lower probability of remission (p < .05). (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Antidepressant‐induced sexual dysfunction

Sexual dysfunction is a frequent, potentially distressing, adverse effect of antidepressants and a leading cause of medication non-adherence. Sexual function should be actively assessed at baseline, at regular intervals during treatment, and after treatment cessation. Trials comparing the risk of sexual dysfunction with individual antidepressants are inadequate, but it is reasonable to conclude that the risk is greatest with selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs), less with tricyclic antidepressants (except clomipramine) and mirtazapine, and least with moclobemide, agomelatine, reboxetine and bupropion. Management of antidepressant-induced sexual dysfunction requires an individualised approach (eg, considering other causes, dose reduction, addition of medication to treat the adverse effect, switching to a different antidepressant). Post-SSRI sexual dysfunction has been recently identified as a potential, although rare, adverse effect of SSRIs and SNRIs. Consider the possibility of post-SSRI sexual dysfunction in patients in whom sexual dysfunction was absent before starting antidepressants but develops during or soon after antidepressant treatment and still persists after remission from depression and discontinuation of the drug.

Effects of antidepressant and antipsychotic use on weight gain: A systematic review.

Weight gain is an adverse effect of antidepressants and antipsychotics. This side effect can lead to numerous comorbidities and reduces life expectancy. The use of these drugs is increasing worldwide, and the weight gain produced by them represents a common clinical challenge. The goal of this systematic review was to evaluate the potential association of antidepressant and antipsychotic therapy with body weight gain in cohort studies. A search of cohort studies investigating the association between weight gain and the use of antidepressants and antipsychotics in individuals was conducted through the PubMed database from 1 January 2008 to 31 January 2019 following the PRISMA statement. We found 27 independent eligible cohort studies that included children (2-18 years old) and adult (18-103 years old) subjects. Most of the included studies showed a 5% weight gain in individuals using antidepressant therapy. However, Quetiapine, Haloperidol, Trifluoperazine, Risperidone, Aripiprazole, Olanzapine, and Clozapine increased body weight ≥7% from baseline, which is considered a clinically significant result. Weight loss was found in individuals treated with Bupropion. Further cohort studies with higher sample sizes and longer durations of treatment are needed to confirm our observations.

Efficacy of a standardised saffron extract (affron®) as an add-on to antidepressant medication for the treatment of persistent depressive symptoms in adults: A randomised, double-blind, placebo-controlled study.

As a stand-alone intervention, saffron has efficacy for the treatment of mild-to-moderate depression. However, research as an adjunct agent is limited. The effects of saffron as an adjunct to pharmaceutical antidepressants in adults with persistent depression was investigated. In this eight-week, randomised, double-blind, placebo-controlled study, adults with persistent depression, currently taking a pharmaceutical antidepressant were given a placebo or a saffron extract (affron®, 14 mg b.i.d.). Primary outcome measures included the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) and self-rated MADRS (MADRS-S). Secondary outcome measures included the Antidepressant Side-Effect Checklist (ASEC) and Short Form-36 Health Survey (SF-36). Of the 160 participants enrolled, 139 provided usable data. Based on the MADRS, depressive symptoms decreased more in participants taking saffron compared with a placebo, with reductions of 41 and 21%, respectively (p = 0.001). However, scores on the MADRS-S decreased 27 and 26% in the saffron and placebo conditions, respectively (p = 0.831). Saffron was associated with a greater reduction in adverse effects of antidepressants (p = 0.019), although this was non-significant after covarying for baseline values (p = 0.449). Quality of life improved in both groups with no significant between-group differences (p = 0.638). Adjunctive administration of a standardised saffron extract (affron®) for eight weeks was associated with a greater improvement in depressive symptoms as measured by the clinician-rated MADRS but not the self-report MADRS-S. Given the conflicting results, further research is needed to clarify the clinical benefits of saffron as an adjunctive treatment for adults with persistent depressive symptoms despite antidepressant drug treatment.

Extrapyramidal reactions following treatment with antidepressants: Results of the AMSP multinational drug surveillance programme

Objectives: Extrapyramidal symptoms (EPS) are a common adverse effect of antipsychotics. However, there are case reports describing EPS following treatment with antidepressants. It is not fully understood how antidepressants cause EPS, but a serotonergic input to dopaminergic pathways is a probable mechanism of action.Methods: Data from a multicenter drug-surveillance programme (AMSP, ‘drug safety in psychiatry’) which systemically documents severe drug reactions during psychiatric inpatient admissions, were reviewed to assess for EPS associated with antidepressant treatment. We identified 15 such cases, which were studied to detect similarities and to characterise risk factors.Results: We report on 15 patients with EPS following antidepressant-therapy between 1994 and 2016. EPS frequently occurred with selective serotonin reuptake inhibitor (SSRI) treatment alone (7/15 cases) or concomitant SSRI treatment (6/15 cases). EPS were most frequent with escitalopram-treatment (5 cases). The most common EPS was atypical dyskinesia (6/15 cases) followed by akathisia (4/15 cases). The mean age of onset for EPS was 54.93 years (SD 17.9). EPS occurred at any dosage and equally often in men and women.Conclusions: Our results highlight the possibility of EPS as an important, although uncommon, adverse effect of antidepressants. Clinicians should beware of this adverse effect and monitor early warning signs carefully.

Suicidality rare as adverse effect of antidepressants

A review of data for hospitalized patients taking antidepressants has found that suicidal thoughts and behavior as a consequence of antidepressant use were rare. Suicidal adverse reactions were most likely with use of selective serotonin reuptake inhibitors (SSRIs) and usually occurred early in treatment, researchers found.

SSRI Induced Apathy Syndrome

Objective: Apathy is defined as diminished motivation and reduced goal-directed behavior accompanied by decreased emotional responsiveness. Besides being a symptom of some neurological conditions and psychiatric disorders, apathy is also a known to be an adverse effect of antidepressants. Although attention to antidepressant-induced apathy has been increasing in recent years, studies about apathy are still very limited and generally presented as case reports. Despite being an important cognitive side effect of antidepressants it is not well recognized and may be misinterpreted as a residual symptom of the psychiatric disorder by clinicians. In this study, we aimed to analyze apathy levels of patients with anxiety disorders (AD) and major depressive disorder (MDD) before and after antidepressant treatment, with a prospective design. Methods: Our study included 20 MDD and 20 AD patients admitted to Mersin University Research and Training Hospital, Outpatient Clinic of Psychiatry, who have not taken any antidepressant medication for at least last one month. Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Apathy Evaluation Scale (AES) were administered before antidepressant treatment and on the 6th week of the treatment. Correlations and relationships between scale scores were analyzed. Results: Thirty-five (87,5%) of the 40 patients were taking Selective Serotonin Reuptake inhibitors (SSRIs), while 5 (12,5%) were taking Serotonin-Noradrenalin Reuptake Inhibitors (SNRIs). In the whole group of patients, AES scores increased from a mean of 20,5 at baseline to 25 after antidepressant treatment (p

The Association Between the Severity and Level of Understanding of Depression Among Patients Treated With Antidepressants: A Survey of 424 Outpatients in Japan.

The present study investigated the association between the severity and knowledge of depression and attempted to reveal the specific aspects of understanding associated with severity. A total of 424 outpatients were enrolled in this study. We used an original self-administered questionnaire: (a) the symptoms of depression, (b) the course of depression, (c) the cause of depression, (d) the treatment plan, (e) the duration of antidepressant use, (f) how to discontinue antidepressant use, (g) the adverse effects of antidepressants, and (h) psychotherapy. Each category consisted of the following questions: "How much do you understand about your treatment?" The level of understanding was rated on an 11-point scale ranging from 0 to 10. The following scales were administered: the Quick Inventory of Depressive Symptomatology, Japanese version (QIDS-J); the Global Assessment of Functioning; and the Clinical Global Impression, Severity scale. Subjects were divided in 5 groups according to severity of QIDS-J. Clinical characteristics were also investigated. Based on an analysis of variance, significant differences were found among the 5 groups with regard to age at onset, duration of disease, and duration of antidepressant use. A multiple regression analysis revealed that item B significantly and negatively predicted the QIDS-J scores, whereas item C significantly and positively predicted these scores. Some multiple logistic regression models seeking to distinguish severity found that all but items E to H were significantly associated with severity. Items B and C were significantly negatively and positively associated with depression severity, respectively. Sufficient and suitable psychoeducation in and knowledge of depression might improve the treatment responses in patients with depression.

Adverse effects of antidepressants in children and adolescents

Adverse effects of antidepressants in children and adolescents

Safety of Trazodone in Older People. an Observational Study in Nursing Homes.

Introduction The evaluation of safety represents the our interest, especially with references to older people that receive at the same time many drugs for psychiatric disorders and physical diseases. The polypharmacy between older people is a frequent phenomenon but little is know about adverse effects of antidepressants. Method We have examined the prescriptions in 10 nursing homes to collect adverse effects, included cause mortality, during a follow up of 2 years. Results The incidence of adverse events with Trazodone is very low, as so compared to other antidepressants. Also, older people, are a special population with high comorbidity. Still it is very difficult to reduce the recurrence to polypharmacy in these field but we must become integrated with general practitioners and other specialists.

Reducing the Global Burden of Depression

&lt;p&gt;Depression is expected to be one of the leading causes of morbidity by 2020. Nonetheless, the current methods of treatment for depression may not be effective in reducing the global burden of this disease. Currently, pharmacotherapy represents the first line treatment for depressive disorders; however, many adverse effects of anti-depressants are often overlooked and their interference with body chemistry may not be ideal for long-term treatment.&lt;/p&gt;&lt;p&gt;In order to reduce the burden of disease of depression, methods of treatment such as counseling and therapy should be considered as alternatives to pharmacotherapy. Most importantly, these treatments reduce the occurrence of depression relapse, making them more effective in the long-term. In addition to alternative methods of treatment, depression prevention strategies should be prioritized. Not only is depression prevention the best solution therapeutically, but it is also the most cost-effective in reducing global morbidity. In order to implement these strategies, however, more evidence-based research on the prevention of depressive disorders is required.&lt;/p&gt;

Adverse emotional and interpersonal effects reported by 1829 New Zealanders while taking antidepressants

In the context of rapidly increasing antidepressant use internationally, and recent reviews raising concerns about efficacy and adverse effects, this study aimed to survey the largest sample of AD recipients to date. An online questionnaire about experiences with, and beliefs about, antidepressants was completed by 1829 adults who had been prescribed antidepressants in the last five years (53% were first prescribed them between 2000 and 2009, and 52% reported taking them for more than three years). Eight of the 20 adverse effects studied were reported by over half the participants; most frequently Sexual Difficulties (62%) and Feeling Emotionally Numb (60%). Percentages for other effects included: Feeling Not Like Myself – 52%, Reduction In Positive Feelings – 42%, Caring Less About Others – 39%, Suicidality – 39% and Withdrawal Effects – 55%. Total Adverse Effect scores were related to younger age, lower education and income, and type of antidepressant, but not to level of depression prior to taking antidepressants. The adverse effects of antidepressants may be more frequent than previously reported, and include emotional and interpersonal effects.

Use of antidepressants during pregnancy: a better choice for some.

Mood disorders such as depression are more common among women, especially among pregnant women. Some population-based studies report a 20% prevalence of depression among pregnant women.[1],[2] Given this relatively high prevalence, the use of antidepressant medication during pregnancy is not uncommon. A study in the United States reported that at least 10% of pregnant women used antidepressants during pregnancy.[3] However, antidepressants may interfere with fetal growth so there is an ongoing debate about whether or not antidepressants should be used during pregnancy. Like all medications, antidepressants should be used with caution during pregnancy. The use of anti-depressants during pregnancy has been linked to various negative outcomes including miscarriage, pre-term birth, and low birth weight. One study found that within the two weeks of birth, newborns of mothers who used antidepressants during pregnancy were more likely to develop poor neonatal adaptation syndrome (OR=5.07, 95% CI=3.25-7.90), a condition which is characterized by poor temperature control, hypoglycemia, tachypnoea, respiratory distress, nasal congestion or cyanosis and seizures.[4] A systematic review reported a higher risk of developing congenital heart defects among newborns of mothers who used paroxetine during pregnancy (OR=1.36, 95% CI=1.08-1.71); however, this study did not find evidence of an overall association between the use of antidepressants and neonatal birth defects.[5] Untreated depression during pregnancy has been linked to more pre-term births and less breast-feeding.[6] Depression during pregnancy has also been associated with asthma in newborns, and the severity of depression was positively correlated with the severity of asthma (a dose-response relationship).[7] Moreover, the distress experienced by women with depression who are pregnant is similar to that experienced by women with depression who are not pregnant; the decline in their quality of life, impairment in their social functioning, and their risk of suicide are the same.[8] Therefore, treatment of depression during pregnancy is important for both the mother and the child. Psychotherapy, specifically interpersonal psycho-therapy,[9] has been shown to ameliorate depressive mood in pregnant women. However, this has only been studied among pregnant women with mild to moderate depression, not among those with severe depression for whom antidepressant treatment may be necessary. To date, there has been limited evidence about the effectiveness and safety of antidepressant use during pregnancy. Some experts have reached a consensus that antidepressants should be used to treat severe depression during pregnancy.[10] The Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults suggest weighing the adverse effects of antidepressants on the fetus (which occur at a low frequency) against the benefits of treatment. The guidelines list fluoxetine and other selective serotonin re-uptake antidepressants (SSRIs) as first-line antidepressants for use during pregnancy, but they also warn of possible neonatal heart defects after the use of fluoxetine.[11] A small-sample prospective study compared neonatal outcomes between 35 pregnant women who used antidepressants (mainly SSRI) with 23 pregnant women who did not. This study found no differences in cognitive functioning, language, and mobility in the babies at 18 months of age.[12] Another case report found no anomalies in the physical or mental development of a nine-month-old infant born to a mother who had taken duloxetine.[13] We believe that the benefits of antidepressant treatment of pregnant women with depression out-weigh the possible risk to the fetus: (a) if the depression is severe (that is, with suicidal ideation or behavior, psychotic symptoms, or a complete loss of appetite), (b) if there is a family history of re-occurring mental disorders, (c) if the individual lacks family or social support, or (d) if moderate depression persists despite psychotherapeutic treatment. Antidepressant use should be considered for the treatment of pregnant women who meet any of these criteria. The pros and cons of antidepressant treatment should be discussed with the individuals and their family members before obtaining their informed consent. Currently, most guidelines recommend the use of SSRIs (e.g., fluoxetine and citalopram) or tricyclic antidepressants (e.g., nortriptyline) for depression during pregnancy. Psychiatrists should ensure that the depressed woman and her family members are aware of the potential risks and immediately report any related symptoms. Psychiatrists treating pregnant women also need to coordinate their treatment with the responsible obstetrician to ensure the timely prevention of possible negative outcomes.

ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder

P-glycoprotein (P-gp), an ATP-driven efflux pump in the blood-brain barrier, has a major impact on the delivery of antidepressant drugs in the brain. Genetic variants in the gene ABCB1 encoding for P-gp have inconsistently been associated with adverse effects. In order to resolve these inconsistencies, we conducted a study in a large cohort of patients with major depressive disorder with the aim to unravel the association of ABCB1 variants with adverse effects of antidepressants and in particular with selective serotonin reuptake inhibitors (SSRIs), which display affinity as substrate for P-gp. The Netherlands Study of Depression and Anxiety (NESDA) study was used as a clinical sample. For 424 patients data were available on drug use, side effects. We selected six ABCB1 gene variants (1236T>C, 2677G>T/A, 3435T>C, rs2032583, rs2235040 and rs2235015) and analyzed them for association with adverse drug effects using multinomial regression analysis for both single variants and haplotypes. We found a significant association between the number of SSRI-related adverse drug effects and rs2032583 (P=0.001), rs2235040 (P=0.002) and a haplotype (P=0.002). Moreover, serotonergic effects (sleeplessness, gastrointestinal complaints and sexual effects) were significantly predicted by these variants and haplotype (P=0.002/0.003). We conclude that adverse drug effects with SSRI treatment, in particular serotonergic effects, are predicted by two common polymorphisms of the ABCB1 gene.