Long-term Antidepressant Use Research Articles

Cost-utility analysis of a treatment advice to discontinue inappropriate long-term antidepressant use in primary care.

Antidepressant prescriptions have increased exponentially, burdening health care costs. To evaluate the costs and effects of an antidepressant cessation advice in case of inappropriate long-term use in primary care, i.e. long-term usage without a (current) indication. A economic evaluation during 1-year follow-up was performed, from a societal perspective, as part of a cluster-randomised controlled clinical trial (PANDA). Costs were assessed using the Trimbos/iMTA questionnaire for costs associated with psychiatric illness. Health-related quality of life was measured using the EuroQol 5D. Outcome was costs per quality adjusted life year (QALY). Missing values were estimated using multiple imputation, bootstrap simulations were performed to address the uncertainty surrounding the incremental cost-effectiveness ratios (ICERs). There was no difference in average QALYs between the intervention (0.70) and control group (0.72) [difference -0.02 (95% CI -0.05 to 0.10)]. The intervention group, however, was less expensive than the control group (total costs €3636 versus €5267, respectively). Most cost-effectiveness pairs were located in the south-west quadrant of the cost-effectiveness plane, implying the intervention was less effective but also less costly. The ICER of the pooled data was €70,180, meaning that for one QALY lost, €70,180 is saved. This study shows that an antidepressant cessation advice given to patients (and their FPs) with inappropriate long-term antidepressant usage, albeit not effective, does seem to result in a reduction of societal costs. This reduction in costs is mostly due to reduction of productivity losses, possibly due to patient empowerment and loss of stigma.

Dimorphic changes of some features of loving relationships during long-term use of antidepressants in depressed outpatients

The present study aimed at investigating the possible changes of some features of loving relationships during long-term treatment of depression with both selective serotonin reuptake inhibitors (SSRIs) and tricyclics (TCAs), by means of a specifically designed test, the so-called “Sex, Attachment, Love” (SALT) questionnaire.The sample was composed by 192 outpatients (123 women and 69 men, mean age±SD: 41.2±10.2 years), suffering from mild or moderate depression, according to DSM-IV-TR criteria, that were selected if they were treated with one antidepressant only for at least six months and were involved in a loving relationship.The results showed that SSRIs had a significant impact on the feelings of love and attachment towards the partner especially in men, while women taking TCAs complained of more sexual side effects than men. These data were supported also by the detection of a significant interaction between drug and sex on the “Love” and “Sex” domains.The present findings, while demonstrating a dimorphic effect of antidepressants on some component of loving relationships, need to be deepened in future studies.

Long-Term Antidepressant Use and the Risk of Type 2 Diabetes Mellitus

Antidepressant drugs might induce weight gain and increase diabetes risk. We examined the diabetes risk with long-term antidepressant use in a general population. This study was a population-based, nested case-control study using Taiwan's National Health Insurance Research Database between 1998 and 2009. A total of 47,885 patients with type 2 diabetes mellitus (ICD-9 codes: 250.x; excluding 250.x 1 and 250.x 3) and 95,770 controls were identified. We used a conditional logistic regression model for data analysis and 1-year latent period before the diabetes diagnosis to account for the quantification of treatment duration of antidepressant (defined by Anatomic Therapeutic Chemical classification code N06A). Sensitivity analyses were performed using a propensity score matching method, as well as different lengths of latent periods. Compared with nonusers, patients with cumulative antidepressant use (> 2 years) had an increased risk of diabetes (adjusted OR = 1.20; 95% CI, 1.05-1.37). Moreover, increasing mean daily dose or use of selective serotonin reuptake inhibitors or serotonin antagonist and reuptake inhibitors was associated with increased diabetes risk. The increased diabetes risk with long-term antidepressant therapy in patients aged 44 years or less (adjusted OR = 2.39; 95% CI, 1.46-3.90) was higher than that in older adults (adjusted OR = 1.15; 95% CI, 1.00-1.32). The findings suggest that long-term antidepressant use may be associated with an increased risk of type 2 diabetes mellitus, especially for young adults. Therefore, long-term antidepressant use should be evaluated more cautiously for its benefits and the potential risk of diabetes.

National Trends in Long-Term Use of Antidepressant Medications

To assess the trend in long-term use of antidepressants by persons aged ≥ 18 years, and the correlates of such use, in the United States from 1999 to 2010. We examined trends in duration of antidepressant use and correlates of long-term use in data from 6 waves of the cross-sectional National Health and Nutrition Examination Survey (N = 35,379), a representative survey of the general population. The overall prevalence of antidepressant use increased from 6.5% in 1999-2000 to 10.4% in 2009-2010 (odds ratio [OR] = 1.54; 95% CI, 1.31-1.81; P < .001). This included an increase from 3.0% to 6.9% in long-term use (≥ 24 months; OR = 2.12; 95% CI, 1.75-2.57; P < .001). Medium-term (6 to < 24 months; from 1.3% to 1.6%) and short-term use (< 6 months; from 2.2% to 1.8%) of antidepressants did not change appreciably in this period. The increasing trend in long-term antidepressant use was limited to adults who received their care from general medical providers (adjusted OR = 3.86; 95% CI, 2.57-5.80; P < .001). From 1999 to 2010, there was a marked increase in long-term use of antidepressant medications in the United States, explaining the overall increasing trend in antidepressant use. This trend calls for greater vigilance in prescribing antidepressants for long periods of time.

Antidepressants for bipolar disorder: A meta-analysis of randomized, double-blind, controlled trials.

OBJECTIVE:To examine the efficacy and safety of short-term and long-term use of antidepressants in the treatment of bipolar disorder.DATA SOURCES:A literature search of randomized, double-blind, controlled trials published until December 2012 was performed using the PubMed, ISI Web of Science, Medline and Cochrane Central Register of Controlled Trials databases. The keywords “bipolar disorder, bipolar I disorder, bipolar II disorder, bipolar mania, bipolar depression, cyclothymia, mixed mania and depression, rapid cycling and bipolar disorder”, AND “antidepressant agent, antidepressive agents second- generation, antidepressive agents tricyclic, monoamine oxidase inhibitor, noradrenaline uptake inhibitor, serotonin uptake inhibitor, and tricyclic antidepressant agent” were used. The studies that were listed in the reference list of the published papers but were not retrieved in the above-mentioned databases were supplemented.STUDY SELECTION:Studies selected were double-blind randomized controlled trials assessing the efficacy and safety of antidepressants in patients with bipolar disorder. All participants were aged 18 years or older, and were diagnosed as having primary bipolar disorder. Antidepressants or antidepressants combined with mood stabilizers were used in experimental interventions. Placebos, mood stabilizers, antipsychotics and other antide pressants were used in the control interventions. Studies that were quasi-randomized studies, or used antidepressants in combination with antipsychotics in the experimental group were excluded. All analyses were conducted using Review Manager 5.1 provided by the Cochrane Collaboration.MAIN OUTCOME MEASURES:The primary outcome was the response and switching to mania. The secondary outcomes included remission, discontinuation rate, and suicidality.RESULTS:Among 5 001 treatment studies published, 14 double-blind randomized controlled trials involving 1 244 patients were included in the meta-analysis. Eleven short-term studies and three maintenance studies were included. Studies suggested that patients treated with antidepressants were not significantly more likely to achieve higher response and remission rates in the short-term or long-term treatment than patients treated with placebo and other medications. Antidepressants were not associated with an increased risk of discontinuation, relapse or suicidality. When one antidepressant was compared with another, no significant difference in efficacy and tolerability was found.CONCLUSION:Existing evidence of efficacy does not support the short-term or long-term application of antidepressant therapy in patients with bipolar disorder, although the tolerability and safety of antidepressants have been generally acknowledged. There is a need for large-sample, double-blind, randomized controlled trials to elucidate the role of antidepressants in patients with different subcategories of bipolar disorder.

Side effects of antidepressants during long-term use in a naturalistic setting

Side effects of antidepressants are usually underreported in clinical trials and large scale naturalistic studies are restricted to six months of use. We examined the prevalence and nature of patient-perceived side effects and their determinants during long-term antidepressant use in a naturalistic setting. Subjects, aged 19 to 67 years, in the Netherlands Study of Depression and Anxiety were recruited from primary care and specialized mental health care covered 927 cases of single antidepressant use. In 64% of cases, on average, 2.9 side effects were reported. The number of side effects was higher when subjects had higher depression severity (OR=1.28; p=0.002), three or more psychiatric diagnoses (OR=1.97; p=0.02), higher dose (OR=1.44; p=0.006) and was lower when subjects were older (OR=0.83; p=0.02) and had longer duration of use (OR=0.94; p=0.04). Tricyclic antidepressants were associated with more side effects (OR=2.52; p=0.003) and, particularly, more anticholinergic effects, like dry mouth and constipation, as compared to selective serotonin reuptake inhibitors. Venlafaxine showed more profuse sweating (OR=1.79; p=0.007), whereas mirtazapine showed more weight gain and less sexual dysfunction (OR=0.36; p=0.03), as compared to selective serotonin reuptake inhibitors. Weight gain was associated with female gender (OR=1.76; p=0.004) and duration of use (OR=1.06; p=0.03). We show that antidepressant side effect, known from short-term studies, persist during long-term use and are associated with depression severity and antidepressant dose. A novel finding was that venlafaxine is associated with more profuse sweating and that weight gain appeared more specific in female users. Clinicians should be aware that, during long-term antidepressant use, side effects are common and persistent.

Antidepressant use, depression, and new-onset diabetes among elderly Medicare beneficiaries.

The aim of the present study was to examine the association between antidepressant use, diagnosed depression, and new-onset diabetes among elderly Medicare beneficiaries. Longitudinal data from merged survey and claims from the nationally representative Medicare Current Beneficiary Survey(MCBS) from 1999 to 2005 were used. Diabetes incidence was extracted from claims and survey data over a 3-year period. Data regarding depression and antidepressant use over time were obtained. Multivariate logistic regression analysis was used to examine associations between antidepressant use, depression, and new-onset diabetes, adjusted for demographic, socioeconomic, and lifestyle risk factors. Analyses accounted for the complex design of the MCBS. The incident diabetes rate was 4.8% for those "without depression and without antidepressants" and 9.5% for those with any antidepressant use in all 3 years and diagnosed depression". Compared with Medicare beneficiaries who did not report any antidepressant use, beneficiaries reporting antidepressant use in all 3 years were 50% more likely to have new-onset diabetes. However, when diagnosed depression was entered in the model, there was no significant association between long-term antidepressant use and new-onset diabetes. Medicare beneficiaries with any depression were twice as likely as those without depression to develop diabetes (adjusted odds ratio 2.04; 95% confidence interval 1.51, 2.75). Depression independently increased the risk of developing diabetes in the MCBS population, although there is no evidence of an association between antidepressant use and new-onset diabetes. If replicated, these results have significant clinical implications.

Poststroke depression: prevalence, pathogenesis, diagnosis, and treatment

The paper reviews the data available in the literature on the prevalence, pathogenesis, diagnosis, treatment, and prevention of poststroke depression. Depression develops in nearly one in every three patients, who have experienced stroke, and can negatively affect the rehabilitation process. The role of psychological factors, genetic predisposition, brain lesion location, monoamine deficiency in the pathogenesis of depression is considered. Poststroke depression is frequently diagnosed although it is detected using simple studies (Beck depression inventory, Hamilton rating scale). Psychotherapy is effective in preventing poststroke depression; the efficacy of antidepressants is actively being investigated. When depression develops, there is a positive result of treatment with antidepressants; a combination of psychotherapy and antidepressants produces even a more pronounced effect. The long-term (6-month or more) use of tricyclic antidepressants and selective serotonin reuptake inhibitors is noted to have a positive effect; there are data on the high efficacy and good tolerability of escitalopram in poststroke depression. It is stressed that the prevention and treatment of depression may substantially improve the rehabilitation process and quality of life.

Pharmacology for the Treatment of Premature Ejaculation

Male sexual response comprises four phases: excitement, including erection; plateau; ejaculation, usually accompanied by orgasm; and resolution. Ejaculation is a complex sexual response involving a sequential process consisting of two phases: emission and expulsion. Ejaculation, which is basically a spinal reflex, requires a tight coordination between sympathetic, parasympathetic, and somatic efferent pathways originating from different segments and area in the spinal cord and innervating pelvi-perineal anatomical structures. A major relaying and synchronizing role is played by a group of lumbar neurons described as the spinal generator of ejaculation. Excitatory and inhibitory influences from sensory genital and cerebral stimuli are integrated and processed in the spinal cord. Premature ejaculation (PE) can be defined by ≤1-min ejaculatory latency, an inability to delay ejaculation, and negative personal consequences. Because there is no physiological impairment in PE, any pharmacological agent with central or peripheral mechanism of action that is delaying the ejaculation is a drug candidate for the treatment of PE. Ejaculation is centrally mediated by a variety of neurotransmitter systems, involving especially serotonin and serotonergic pathways but also dopaminergic and oxytocinergic systems. Pharmacological delay of ejaculation can be achieved either by inhibiting excitatory or reinforcing inhibitory pathways from the brain or the periphery to the spinal cord. PE can be treated with long-term use of selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. Dapoxetine, a short-acting SSRI, is the first treatment registered for the on-demand treatment of PE. Anesthetics applied on the glans penis have the ability to lengthen the time to ejaculation. Targeting oxytocinergic, neurokinin-1, dopaminergic, and opioid receptors represent future avenues to delaying ejaculation.

RETRACTED ARTICLE: Use of antidepressants and the risk of type 2 diabetes mellitus: a nested case–control study

Recent evidence from case reports, observational studies, and randomized trials suggests that long-term use of antidepressants increases the risk of developing diabetes. However, the nature of the relationship between antidepressants and diabetes remains unclear. To determine whether there is an association between antidepressant use and the risk of developing type 2 diabetes mellitus. A nested case-control study using the Texas Medicaid prescription claims database was conducted. Data were extracted for new users of either antidepressant agents (exposed) or benzodiazepines (unexposed) from January 1, 2002 through December 31, 2009. Patients aged 18-64 years without a history of diabetes were included in the cohort. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the risk of diabetes associated with antidepressant exposure was computed using conditional logistic regression, controlling for demographic and clinical covariates. Development of type 2 diabetes mellitus. Among the total sample (N = 44,715), the majority were in the exposed (N = 35,552) vs. the unexposed (N = 9,163) group. A total of 2,943 cases of type 2 diabetes mellitus and 11,748 matched controls (1:4) were identified using risk-set sampling. Cases and controls were matched using age and gender. Antidepressant use was associated with an increase in the risk of (type-2) diabetes when compared to benzodiazepine use [Adjusted Odds Ratio (OR) = 1.512; 95% CI 1.345-1.700]. The association was observed with serotonin-norepinephrine reuptake inhibitors (OR = 1.742; 95% CI 1.472-2.060), tricyclic antidepressants (OR = 1.533; 95% CI 1.295-1.814), selective serotonin reuptake inhibitors (OR = 1.457; 95% CI 1.279-1.659), "Other" antidepressants (OR = 1.318; 95% CI 1.129-1.540). Antidepressant use was associated with an increased risk of (type-2) diabetes. This association was observed for tricyclic antidepressants, serotonin-reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other antidepressants.

Antidepressant drug use and future diabetes risk

Antidepressant drug use and future diabetes risk

A Deficit in Peripheral Serotonin Levels in Major Depressive Disorder but Not in Chronic Widespread Pain

It has been proposed that serotonin dysfunctions underlie the pathophysiology of various mood disorders (including major depressive disorder, MDD) and chronic pain conditions characterized by deficient pain inhibition, such as fibromyalgia (FM). There is reliable data showing that serotonin disturbances are involved in the pathophysiology of MDD. However, in the case of FM, results published so far are less consistent. Therefore, the current cross-sectional study sought to measure plasma serotonin levels in FM patients, MDD patients, and healthy controls (HC). Twenty-nine FM patients, 17 MDD patients, and 57 HC were recruited who did not differ in terms of age, sex, and the presence or absence of a regular menstrual cycle. Plasma samples were analysed with mass spectrometry. Serotonin levels were decreased in MDD patients, relative to FM patients and HC. Post hoc analyses showed that serotonin levels were decreased in FM patients taking antidepressants, relative to HC, but not in drug-free FM patients. Moreover, serotonin levels were negatively correlated with mood symptoms across groups. Our results further confirm that MDD is associated with decreased serotonin levels, but that serotonin levels are not altered in FM per se, and suggest that 5-Hydroxytryptamine is related to mood symptoms in these patient groups. Our results also suggest that the taking of antidepressant is a major confound to consider when studying serotonin functioning in FM. The long-term use of antidepressants in FM may lead to serotonin depletion. Conversely, serotonin depletion may be before the taking of antidepressants in FM.

Do Antidepressants Raise the Risk of Stroke?

Do Antidepressants Raise the Risk of Stroke?

Tardive dysphoria: antidepressant-induced chronic depression.

A significant number of depressed individuals experience inadequate benefit from long-term antidepressant use. This paper investigates the hypothesis that in some individuals persistent use of antidepressants may be prodepressant. Literature regarding the effect of long-term use of antidepressants was reviewed by searching PubMed and Ovid data bases with terms: antidepressant tachyphylaxis, treatment-resistant depression, chronic depression and antidepressant tolerance. Antidepressant treatment-resistant patients frequently had a positive initial response to antidepressants. When resistance appeared, initial increases in dose or medication changes usually resulted in transient improvement. Eventually, the episodic course of the original depressive illness was replaced with a continuous, unresponsive depressive syndrome. We propose the term tardive dysphoria to describe this phenomenon. The phenomenon of antidepressantinduced depression, or tardive dysphoria, needs to be experimentally examined in blinded, randomised antidepressant discontinuation studies.

Disrupting the rhythm of depression: design and protocol of a randomized controlled trial on preventing relapse using brief cognitive therapy with or without antidepressants

BackgroundMaintenance treatment with antidepressants is the leading strategy to prevent relapse and recurrence in patients with recurrent major depressive disorder (MDD) who have responded to acute treatment with antidepressants (AD). However, in clinical practice most patients (up to 70-80%) are not willing to take this medication after remission or take too low dosages. Moreover, as patients need to take medication for several years, it may not be the most cost-effective strategy. The best established effective and available alternative is brief cognitive therapy (CT). However, it is unclear whether brief CT while tapering antidepressants (AD) is an effective alternative for long term use of AD in recurrent depression. In addition, it is unclear whether the combination of AD to brief CT is beneficial.Methods/designTherefore, we will compare the effectiveness and cost-effectiveness of brief CT while tapering AD to maintenance AD and the combination of CT with maintenance AD. In addition, we examine whether the prophylactic effect of CT was due to CT tackling illness related risk factors for recurrence such as residual symptoms or to its efficacy to modify presumed vulnerability factors of recurrence (e.g. rigid explicit and/or implicit dysfunctional attitudes). This is a multicenter RCT comparing the above treatment scenarios. Remitted patients on AD with at least two previous depressive episodes in the past five years (n = 276) will be recruited. The primary outcome is time related proportion of depression relapse/recurrence during minimal 15 months using DSM-IV-R criteria as assessed by the Structural Clinical Interview for Depression. Secondary outcome: economic evaluation (using a societal perspective) and number, duration and severity of relapses/recurrences.DiscussionThis will be the first trial to investigate whether CT is effective in preventing relapse to depression in recurrent depression while tapering antidepressant treatment compared to antidepressant treatment alone and the combination of both. In addition, we explore explicit and implicit mediators of CT.Trial registrationNetherlands Trial Register (NTR): NTR1907

Increase in the duration of antidepressant treatment from 1994 to 2003: a nationwide population‐based study from Finland

We examined the length and continuity of antidepressant treatment and factors associated with long-term of treatment among adults. Nationwide data from all reimbursed antidepressant prescriptions in 1994-2003 were linked with patients' data retrieved from Statistics Finland and the Finnish Hospital Discharge Register. Logistic regression models were used to analyse long term use of antidepressants. The annual prevalence of antidepressant use increased from 3.6% in 1994 to 7.3% in 2003. Short-term use (<3 months) decreased from 58% in 1995 to 51% in 2000 and long-term treatment (≥12 months) increased from 18 to 21%. In 2000, 31% of treatment periods lasted ≥6 months and 24% ≥9 months. Long-term treatment correlated to the purchase of other psychotropics, in-patient psychiatric care, and prescription by a psychiatrist. Treatment periods with antidepressants have become longer over time. Clinical factors related to mental disorder severity predict long-term use. Only a quarter had the treatment duration recommended by clinical guidelines for depression.

Depression and Diabetes: More on What the Relationship Might Be

Depression and Diabetes: More on What the Relationship Might Be

Long-Term Antidepressant Use and Risk for Diabetes: Cause for Concern and Optimism

Back to table of contents Previous article Next article Letters to the EditorFull AccessLong-Term Antidepressant Use and Risk for Diabetes: Cause for Concern and OptimismRIPU D. JINDAL M.D.,RIPU D. JINDAL M.D.Search for more papers by this author,Published Online:1 Sep 2009https://doi.org/10.1176/appi.ajp.2009.09050629AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: I commend Frank Andersohn, M.D., et al. (1) for their article, published in the May 2009 issue of the Journal , which examined the risk of diabetes with long-term use of antidepressants. The evidence for overall increased risk with antidepressant use is a cause for concern, but it is heartening to see evidence for differential effects of individual agents, especially the possibility that three commonly used antidepressants, citalopram, fluoxetine, and sertraline, may not increase the risk for diabetes. The authors provided several reasons for their findings. I feel that three additional aspects also merit consideration. First, development of diabetes is determined by two equally important variables, insulin resistance and insulin secretion; the former correlates well with weight and the latter does not (2) . Second, even within a class, individual antidepressants differ in their binding affinity at different receptors (3) . Third, different receptors are known to mediate insulin resistance and insulin secretion; binding at the H 1 and 5-HT 2 C receptors mediates weight and insulin resistance, whereas M 3 muscarinic receptors in the pancreatic β cells play a critical role in regulating insulin secretion (4) . Among the selective serotonin reuptake inhibitors (SSRIs), paroxetine has the greatest affinity at M 3 muscarinic receptors (3) , which may explain its increased diabetogenic risk. Development of diabetes in the absence of weight gain among some users of antidepressants (5) may also be explained by separate receptor systems mediating insulin resistance and secretion. Because of its high M 3 receptor affinity, it is not surprising to see greater rates of diabetes with paroxetine even in the absence of weight gain. Despite mounting evidence of the differential effects of antidepressants within a class, we continue to persist with the current classification. In their abstract, Dr. Andersohn et al. noted that increased risk of diabetes was observed with long-term use of tricyclic antidepressants and SSRIs but did not mention that three SSRIs, sertraline, citalopram, and fluoxetine, were not associated with greater risk for diabetes. Undoubtedly, their results need replication, but it is possible that good news got buried under the bad news.Classifications can be misleading. With the growing understanding of differential effects of antidepressants within a class, it is time we stop assigning “guilt by association.”Ottawa, Ontario, CanadaThe author reports no competing interests.This letter (doi: 10.1176/appi.ajp.2009.09050629) was accepted for publication in June 2009.

Review: long term use of antidepressants for bipolar disorder reduces depressive episodes but increases risk of mania

Review: long term use of antidepressants for bipolar disorder reduces depressive episodes but increases risk of mania

Long-Term Use of Antidepressants for Depressive Disorders and the Risk of Diabetes Mellitus

Use of antidepressants has been reported to cause considerable weight gain. The aim of this study was to assess the risk of diabetes mellitus associated with antidepressant treatment and to examine whether the risk is influenced by treatment duration or daily dose. This was a nested case-control study in a cohort of 165,958 patients with depression who received at least one new prescription for an antidepressant between January 1, 1990, and June 30, 2005. Data were from from the U.K. General Practice Research Database. Patients were at least 30 years of age and without diabetes at cohort entry. A total of 2,243 cases of incident diabetes mellitus and 8,963 matched comparison subjects were identified. Compared with no use of antidepressants during the past 2 years, recent long-term use (>24 months) of antidepressants in moderate to high daily doses was associated with an increased risk of diabetes (incidence rate ratio=1.84, 95% CI=1.35-2.52). The magnitude of the risk was similar for long-term use of moderate to high daily doses of tricyclic antidepressants (incidence rate ratio=1.77, 95% CI=1.21-2.59) and selective serotonin reuptake inhibitors (incidence rate ratio=2.06, 95% CI=1.20-3.52). Treatment for shorter periods or with lower daily doses was not associated with an increased risk. Long-term use of antidepressants in at least moderate daily doses was associated with an increased risk of diabetes. This association was observed for both tricyclic antidepressants and selective serotonin reuptake inhibitors.