Selective Serotonin Reuptake Inhibitor Discontinuation Research Articles

Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation.

Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation. We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice. Male mice received paroxetine (10mg/kg/day, s.c.) for 12days, then were swapped to saline injections for a 13day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system. Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation. This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms.

Reasons for Discontinuation or Change of Selective Serotonin Reuptake Inhibitors in Online Drug Reviews

Selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed medication class to treat a variety of mental disorders. However, adherence to SSRIs is low, and uncovering the reasons for discontinuation among SSRI users is an important first step to improving medication persistence. To identify the reasons SSRIs are discontinued or changed, as reported by patients and caregivers in online drug reviews. This qualitative study used natural language processing and machine learning to extract mentions of changes in SSRI intake from 667 drug reviews posted on the online health forum WebMD from September 1, 2007, to August 31, 2021. The type of medication change, including discontinuation, switch to another medication, or dose change and the reason for the change were manually annotated. In each instance in which an adverse event was reported, the event was categorized using Medical Dictionary for Regulatory Activities primary system organ class (SOC) codes, and its relative frequency was compared with that in spontaneous reporting systems maintained by the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency. Reasons for SSRI medication change as assessed using SOC codes. In total, 667 reviews posted by 659 patients or caregivers (516 [78%] of patients were female; 410 [62%] 25-54 years of age) were identified that indicated a medication change: 335 posts indicated SSRI discontinuation, 188 posts indicated dose change, and 179 posts indicated switched medications. Most authors 625 (95%) were patients. The most common reason for medication discontinuation or switching was adverse events experienced, and the most common reason for dose change was titration. Both uptitration and downtitration were initiated by either a health care professional or patient. The most common adverse events were classified by SOC codes as psychiatric disorders, including insomnia, loss of libido, and anxiety. Compared with those in regulatory data, psychiatric adverse events, adverse events recorded by investigations (mostly weight gain) and adverse events associated with the reproductive system (mostly erectile dysfunction) were reported disproportionately more often. This qualitative study of online drug reviews found that useful information was provided directly by patients or their caregivers regarding their medication behavior, specifically, information regarding SSRI treatment changes that may inform interventions to improve adherence. These findings suggest that these reported adverse events may be associated with SSRI persistence and that people may feel more inclined to report such events on social media than to clinicians or regulatory agencies.

Selective Serotonin Reuptake Inhibitors and Associated Bleeding Risks: A Narrative and Clinical Review.

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study.

Effect of selective serotonin reuptake inhibitor discontinuation on anxiety-like behaviours in mice.

Background:Abrupt cessation of therapy with a selective serotonin reuptake inhibitor (SSRI) is associated with a discontinuation syndrome, typified by numerous disabling symptoms, including anxiety. Surprisingly, little is known of the behavioural effect of SSRI discontinuation in animals.Aim:Here, the effect of SSRI discontinuation on anxiety-like behaviour was systematically investigated in mice.Methods:Experiments were based on a three-arm experimental design comprising saline, continued SSRI and discontinued SSRI. Mice were assessed 2 days after SSRI discontinuation over a 5-day period using the elevated plus maze (EPM) and other anxiety tests.Results:An exploratory experiment found cessation of paroxetine (12 days) was associated with decreased open-arm exploration and reduced total distance travelled, in male but not female mice. Follow-up studies confirmed a discontinuation effect on the EPM in male mice after paroxetine (12 days) and also citalopram (12 days). Mice receiving continued paroxetine (but not citalopram) also showed decreased open-arm exploration but this was dissociable from the effects of discontinuation. The discontinuation response to paroxetine did not strengthen after 28 days of treatment but was absent after 7 days of treatment. A discontinuation response was not discernible in other anxiety and fear-learning tests applied 3–5 days after treatment cessation. Finally, discontinuation effects on the EPM were typically associated with decreased locomotion on the test. However, separate locomotor testing implicated anxiety-provoked behavioural inhibition rather than a general reduction in motor activity.Conclusion:Overall, this study provides evidence for a short-lasting behavioural discontinuation response to cessation of SSRI treatment in mice.

Clinical Utility of Semistructured Interview and Scales to Assess Withdrawal Syndromes With Dose Reduction or Discontinuation of Selective Serotonin Reuptake Inhibitors or Serotonin Norepinephrine Reuptake Inhibitors.

Withdrawal syndromes can occur after dose reduction or discontinuation of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Few measurement instruments are available to assess them: Diagnostic Clinical Interview for Drug Withdrawal 1-New Symptoms of SSRI and SNRI (DID-W1) and Discontinuation Emergent Signs and Symptoms (DESS) checklist. We assessed their interrater reliability, verified the percent agreement between the two, and tested DESS sensitivity and specificity on the basis of the diagnoses formulated via the DID-W1. One-hundred thirty-four subjects who referred for withdrawal at 3 outpatient facilities were enrolled and assessed via the DESS and the DID-W1. Percent agreement and Cohen κ were calculated to measure DID-W1 and DESS interrater reliability, as well as the agreement between DID-W1 and DESS items. Sensitivity and specificity of DESS were derived from the identification of true-positive, false-negative, true-negative, and false-positive on the DID-W1. Both tools showed excellent interrater reliability (DID-W1 Cohen κ = 0.958; DESS Cohen κ = 0.81-1). The degree of agreement between DID-W1 and DESS items was poor or fair (Cohen κ < 0.40) for some items and moderate (Cohen κ = 0.41-0.60) for others. Sensitivity and specificity of DESS were 0.937 (true-positive = 60, false-negative = 4) and 0.285 (true-negative = 20, false-positive = 50), respectively. DID-W1 was a reliable method to identify and diagnose withdrawal syndromes. The DESS checklist showed to be a useful tool for detecting withdrawal SSRI/SNRI symptoms when the aim is to achieve high sensitivity to identify true positives.

Investigation of the efficiency of various antidepressant replacement regimens in the development of SSRI-induced apathy syndrome

Selective serotonin reuptake inhibitors (SSRI)-induced apathy syndrome occurs in 5–20% of patients taking these drugs. Objective: to investigate the possibility and advantages of switching patients with SSRI-induced apathy to treatment with a SSRI and norepinephrine reuptake inhibitor. Patients and methods. The investigation enrolled 105 depressive patients without psychotic symptoms, who were observed to develop symptoms of SSRI-induced apathy during SSRI antidepressant monotherapy for at least 6 months. The patients were randomized to groups: 1) 35 patients were switched to milnacipran (Ixel 50–100 mg/day) with simultaneous antidepressant replacement; 2) 35 patients were prescribed milnacipran with a 2-week gradual discontinuation of the previous SSRI; 3) 35 patients were switched to combined therapy with milnacipran 50–100 mg/day and sulpiride (Eglonyl 50 mg/day). The latter was prescribed to test the hypothesis for the benefits of combined correction of SSRI-induced apathy syndrome. The duration of the investigation was 3 months. Changes in the condition of the patients were assessed during their visits before and 1, 2, 4, 8, and 12 weeks after changing therapy. The efficiency of antidepressant therapy was studied using the 21-item Hamilton Depression Rating Scale (HDRS-21) and the Clinical Global Impression (CGI) rating scale; the changes in the severity of asthenic manifestations were examined according to a subjective asthenia assessment (Multidimensional Fatigue Inventory (MFI-20)). The UKU side effect rating scale was used to verify side effects. Results and discussion. A significant (p<0.05) pronounced thymoleptic effect of various treatment regimens (simultaneous and gradual replacement with monnacipran monotherapy, as well as a milnacipran-sulpiride combination) was confirmed at week 4 of treatment. There was a reduction in SSRI-induced apathy syndrome when switching to treatment with milnacipran or milnacipran-sulpiride in 71.4–80% of patients. Different therapy replacement regimens showed varying changes in the reduction of heterogeneous asthenoapathic symptoms. A favorable safety profile was established for both monotherapy with milnacipran and its combination with sulpiride. Conclusion. The antidepressant milnacipran (up to 100 mg/day) exhibits a high efficacy and a good tolerance in case of SSRI-induced apathy syndrome, as well as by a pronounced thymoleptic effect, including when combined with the antipsychotic sulpiride (50 mg/day).

REM SLEEP DISORDERS IN LEWY BODY DISEASE—OR MAY THERE BE ANOTHER REASON?

In 2017 a 68 year old patient came together with his wife to our outpatient memory department to have his cognitive functions evaluated. The wife complained about a very annoying aggressive sleep behavior, e.g. boxing in the night. This aggressive sleep disorder had been present for about one year. On inspection the patient showed movement disorders like in Parkinson's disease. Patient history, medication and other exams were collected. Moreover neuropsychological tests were done. Apart from an arterial hypertension and a diabetes mellitus type II no further diseases were known. The medication consisted in pantoprazol, citalopram 40 mg once daily, metamizol, candesartan and magnesium. The neurological examination showed a slow moving patient without tremor or rigor and without really typical symptoms for Parkinson's disease. The cognitive testing disclosed deficits in memory and visual construction (for example: clock drawing test score 4, MMSE 23 points, MoCA 17 points). The MRI showed a slight reduction of brain volume and only a few microvascular lesions. The Beta-Cit-SPECT did not point in the direction of Parkinson's disease. In the face of these results Lewy body disease was assumed, where REM sleep disorders are typical. But due to the fact that drugs like selective serotonin reuptake inhibitors (SSRI) may also induce aggressive sleep behavior, the family was advised to first reduce citalopram, but of course slowly to avoid a SSRI discontinuation syndrome. Despite this citalopram the patient discontinued citalopram rapidly and with the end of the citalopram therapy the aggressive sleep disorder disappeared. It was concluded that the first and very evident reason for the REM sleep disorders, the probable Lewy body disease, was not the only reason and that a methodical workup of the patient is important. The Lewy body disease may have laid the ground for a higher susceptibility for REM sleep disorders and that the SSRI had initiated the symptoms.

The Diagnostic clinical Interview for Drug Withdrawal 1 (DID-W1) – New Symptoms of Selective Serotonin Reuptake Inhibitors (SSRI) or Serotonin Norepinephrine Reuptake Inhibitors (SNRI): inter-rater reliability

A wide range of clinical phenomena have been reported with dose reduction or drug discontinuation of Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin Norepinephrine Reuptake Inhibitors (SNRIs). In 2015, a new classification of SRIs/SNRIs withdrawal (i.e., new withdrawal symptoms, rebound symptoms withdrawal, persistent post-withdrawal disorders) was outlined on the basis of the literature and clinical observations. A semistructured clinical interview, the Diagnostic clinical Interview for Drug Withdrawal 1 - New Symptoms of SSRI and SNRI (DID-W1), was developed for identifying and differentiating such syndromes. Its inter-rater reliability has been tested. Seventeen consecutive outpatients with a history of SSRI or SNRI dose reduction or discontinuation were assessed independently by 2 clinicians at different times during the same day. Percent agreement, Cohen’s kappa, and the squared correlation coefficient were used to measure inter-rater reliability. The percent agreement for the whole interview was 97.06%, the Cohen’s kappa 0.85 (95% CI of 0.61-1.08), the squared correlation coefficient 0.72. The kappa values indicated excellent inter-rater agreement. Validity evaluation and comparison with other instruments need to be performed. The DID-W1 may help diagnosing the clinical phenomena related to SSRI and SNRI discontinuation, their differentiation from relapse, and the potential iatrogenic origin of psychiatric symptoms in clinical practice.

Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta-analysis of cohort studies.

We undertook an exclusive meta-analysis of cohort studies investigating the possible link between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and autism spectrum disorders (ASD) in children to further investigate our previous suggestion of confounding by indication. The point estimates regarding the following cohorts were extracted and pooled: (1) pregnant women who discontinued SSRI until 3 months before pregnancy; (2) pregnant women who were exposed to SSRI during pregnancy; and (3) pregnant women with maternal psychiatric disorder but no exposure to SSRI during pregnancy. Although the pooled point estimate of the first cohort showed a trend for increase, it did not reach significance. The pooled point estimates of the latter cohorts showed a significant association with ASD which strengthens our previous suggestion of confounding by indication. Future studies should be adequately designed to differentiate whether the previously suggested association is a result of maternal psychiatric disorder or SSRI exposure or both.

Maternal selective serotonin reuptake inhibitor discontinuation, use, psychiatric disorder and the risk of autism in children: A meta-analysis of cohort studies

Linear ubiquitylation, in which ubiquitin units are covalently linked through N- and C-terminal amino acids, is a unique cellular signaling mechanism. This process is controlled by a single E3 ubiquitin ligase, the linear ubiquitin chain assembly complex (LUBAC), which is composed of three proteins – HOIL-1L, HOIP and SHARPIN. LUBAC is involved in the activation of the canonical NF-κB pathway and has been linked to NF-κB dependent malignancies. In this work, we present HOIP-based stapled alpha-helical peptides designed to inhibit LUBAC through the disruption of the HOIL-1L-HOIP interaction and loss of the functional complex. We find our HOIP peptides to be active LUBAC ubiquitylation inhibitors in vitro, though through interaction with HOIP rather than HOIL. Active peptides were shown to have inhibitory effects on cell viability, reduced NF-κB activity and decreased production of NF-κB related gene products. This work further demonstrates the potential of LUBAC as a therapeutic target and of the use of stapled peptides as inhibitors of protein-protein interactions.

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.

BackgroundApproximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist.Methods/Design‘Stop or Go’ is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk.DiscussionThis study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy.Trial registrationNetherlands Trial Register (NTR): NTR4694; registration date: 16-jul-2014

C.03.03 Pathways to improve cognitive dysfunction in depression

Sexual problems are highly prevalent among patients with psychiatric disorders. They may be caused by the psychopathology of the psychiatric disorder but also by its pharmacotherapy. Both positive symptoms (e.g., psychosis, hallucinations) as well as negative symptoms (e.g., anhedonia) of schizophrenia may negatively interfere with interpersonal and sexual relationships. Atypical antipsychotics have fewer sexual side-effects than the classic antipsychotics. Mood disorders may affect libido, sexual arousal, orgasm, and erectile function. With the exception of bupropion, agomelatine, mirtazapine, vortioxetine, amineptine, and moclobemide, all antidepressants cause sexual side-effects. Selective serotonin reuptake inhibitors (SSRIs) may particularly delay ejaculation and female orgasm, but also can cause decreased libido and erectile difficulties. SSRI-induced sexual side-effects are dose-dependent and reversible. Very rarely, their sexual side-effects persist after SSRI discontinuation. This is often preceded by genital anesthesia. Some personality characteristics are a risk factor for sexual dysfunction. Also patients with eating disorders may suffer from sexual difficulties. So far, research into psychotropic-induced sexual side-effects suffers from substantial methodologic limitations. Patients tend not to talk with their clinician about their sexual life. Psychiatrists and other doctors need to take the initiative to talk about the patient's sexual life in order to become informed about potential medication-induced sexual difficulties.

Chapter 27 - Psychiatric disorders and sexual dysfunction

Sexual problems are highly prevalent among patients with psychiatric disorders. They may be caused by the psychopathology of the psychiatric disorder but also by its pharmacotherapy. Both positive symptoms (e.g., psychosis, hallucinations) as well as negative symptoms (e.g., anhedonia) of schizophrenia may negatively interfere with interpersonal and sexual relationships. Atypical antipsychotics have fewer sexual side-effects than the classic antipsychotics. Mood disorders may affect libido, sexual arousal, orgasm, and erectile function. With the exception of bupropion, agomelatine, mirtazapine, vortioxetine, amineptine, and moclobemide, all antidepressants cause sexual side-effects. Selective serotonin reuptake inhibitors (SSRIs) may particularly delay ejaculation and female orgasm, but also can cause decreased libido and erectile difficulties. SSRI-induced sexual side-effects are dose-dependent and reversible. Very rarely, their sexual side-effects persist after SSRI discontinuation. This is often preceded by genital anesthesia. Some personality characteristics are a risk factor for sexual dysfunction. Also patients with eating disorders may suffer from sexual difficulties. So far, research into psychotropic-induced sexual side-effects suffers from substantial methodologic limitations. Patients tend not to talk with their clinician about their sexual life. Psychiatrists and other doctors need to take the initiative to talk about the patient's sexual life in order to become informed about potential medication-induced sexual difficulties.

Treating Perinatal Depression

Treating Perinatal Depression

Unplanned pregnancy and discontinuation of SSRIs in pregnant women with previously treated affective disorder

ObjectiveTo identify the factors associated with discontinuation of selective serotonin reuptake inhibitors (SSRIs) in pregnant women and to determine the rates of SSRI reintroduction during pregnancy. MethodA prospective study was conducted in the Perinatal Psychiatry Service of the Hospital Clínic in Barcelona. The total sample comprised 132 consecutive pregnant women with depressive or anxiety disorder (DSM-IV criteria), seen between January 2005 and December 2008 and who were receiving SSRIs at the time of conception. Clinical, psychometric and socio-demographic variables were collected at the first visit. All women were assessed during treatment with the Edinburgh Perinatal Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Dose and type of antidepressant were recorded at each visit during pregnancy. ResultsSeventy women (53%) discontinued SSRI treatment upon confirmation of pregnancy. Socio-demographic, obstetric and psychiatric variables did not differ significantly between women who maintained and women who discontinued treatment. Only unplanned pregnancy was associated with a greater risk of discontinuation (OR=2.7, 95% CI=1.34–5.52). Women who discontinued treatment also had higher EPDS and STAI scores in the first visit and prenatal visit (34–36 weeks) (p<.05). Of the 70 women who discontinued treatment, 57.1% (N=40) reintroduced treatment, almost half of these in the first trimester of pregnancy. ConclusionsUnplanned pregnancy was a risk factor for abrupt discontinuation of SSRIs upon confirmation of pregnancy in women with depressive or anxiety disorder. More than half the pregnant women who discontinued SSRIs reintroduced antidepressant therapy during pregnancy.

Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

Besides demonstrated efficacy, selective serotonin reuptake inhibitors (SSRIs) hold other advantages over earlier antidepressants such as greater tolerability and a wider range of clinical applications. However, there is a growing body of clinical evidence which suggests that SSRIs could, in some cases, be associated with a withdrawal reaction upon cessation of regular use. In addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances. Psychological symptoms have also been documented, usually developing within 1–7 days following SSRI discontinuation. The characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs. However, many aspects of the neurobiology of the SSRI discontinuation syndrome (or SSRI withdrawal syndrome) remain unresolved. Following a comprehensive overview of the clinical evidence, we will discuss the underlying pathophysiology of the SSRI discontinuation syndrome and comment on the use of animal models to better understand this condition.

A nationwide prospective study on prescribing pattern of antidepressant drugs in Italian primary care

Our purpose was to explore antidepressant drug (AD) prescribing patterns in Italian primary care. Overall, 276 Italian general practitioners (GPs) participated in this prospective study, recruiting patients >18 years who started AD therapy during the enrolment period (January 2007 to June 2008). During visits at baseline and 3, 6, and 12 months, data about patients' characteristics and AD treatments were collected by the GPs. Discontinuation rate among new users of AD classes [i.e., selective serotonin reuptake inhibitors (SSRI); tricyclics (TCAs); other ADs) were compared. Logistic regression analyses were performed to identify predictors of AD discontinuation. SSRIs were the most frequently prescribed ADs (N = 1,037; 75.3 %), especially paroxetine and escitalopram. SSRIs were more likely to be prescribed because of depressive disorders (80 %), and by GPs (51.1 %) rather than psychiatrists (31.8 %). Overall, 27.5 % (N = 378) of AD users discontinued therapy during the first year, mostly in the first 3 months (N = 242; 17.6 %), whereas 185 (13.4 %) were lost to follow-up. SSRI users showed the highest discontinuation rate (29 %). In patients with depressive disorders, younger age, psychiatrist-based diagnosis, and treatment started by GPs were independent predictors of SSRI discontinuation. In Italy, ADs-especially SSRIs-are widely prescribed by GPs because of depressive/anxiety disorders. Active monitoring of AD users in general practice might reduce the AD discontinuation rate.

WITHDRAWAL OR DEPENDENCE: A MATTER OF CONTEXT

WITHDRAWAL OR DEPENDENCE: A MATTER OF CONTEXT

Economic factors in of patients’ nonadherence to antidepressant treatment

Patients' nonadherence to antidepressant treatment hampers cost and efficacy of depression-specific treatment. However, previous studies have failed to find consistent findings in economic effect on nonadherence and also failed to reach consensus in how to measure nonadherence to treatment. The study attempts to investigate income effect on nonadherence to selective serotonin reuptake inhibitors (SSRIs) treatment with clear definitions of nonadherence: self discontinuation of SSRIs (nonpersistence) and under-dose of SSRIs (noncompliance). The study extracted data from the National Comorbidity Survey-Replication (NCS-R). The study sample (n = 280) includes adults between the ages of 18 and 64 who were diagnosed with Diagnostic Statistics Manual IV Major Depressive Episode (MDE) at some point during their lifetime and medicated with SSRIs in the past 12 months. Just above poverty level of family income and no health insurance increased the risk of medication nonpersistence in SSRIs treatment. The study findings confirmed that African Americans were at higher risk of medication noncompliance than Whites (odds ratio, 4.53) and MDE comorbidity was positively associated with medication noncompliance (odds ratio, 4.25). Low income level, combined with health insurance status, and race/ethnicity, predict nonadherence to antidepressant treatment. The study findings would help physicians and hospitals developing interventional strategies and programs to increase patients' adherence rates in antidepressant treatment.

P-1479 - Unplanned pregnancy, discontinuation of SSRI and risk of relapse

Introduction To our knowledge, only one study has assessed the risk of relapse of affective disorders after discontinuation of antidepressants in pregnancy (Cohen et al, 2006). The factors associated with antidepressant discontinuation are unknown. Objective To describe the factors associated to discontinuation of Selective Serotonin Reuptake Inhibitors (SSRI) in pregnant women and the rates of reintroduction of SSRIs throughout pregnancy. Methods A transversal study was conducted at the Perinatal Psychiatry Program. Total sample was composed by 201 pregnant women with depressive or anxiety disorder (DSM-IV criteria) who received SSRI at the time conception. Clinical and socio-demographic variables were collected at the first visit. Descriptive analysis was performed; categorical variables were compared by using Chi-square statistics or Fisher's exact test and continuous measures were compared by t tests. Results Among the 134 women in the sample, 71 (53%) discontinued treatment with SSRI when they know they are pregnant. Socio-demographic and clinical characteristics did not differ significantly between women who maintain and women who discontinued treatment. Only unplanned pregnancy was associated with major risk of discontinuation treatment (OR 2.86, IC95 1.4–5.7). Also, women who discontinued medication had higher scores on EPDS and STAI (p Nearly 58% (n = 41) of women who discontinued SSRI reintroduced antidepressant therapy during pregnancy, most of them between first and second trimester. Conclusions Unplanned pregnancy was a risk factor for abrupt discontinuation of SSRIs in pregnant women with depressive or anxiety disorder. More than half of pregnant women who discontinued SSRIs reintroduced antidepressant therapy during pregnancy.