antidepressive agents

Pharmacologic Treatment of Perinatal Depression

Megan George — Fri, 21 Nov 2025 19:44:10 +0000

Date Added:

November 21, 2025

Journal/Publication:

JAMA Insights

Publication Date:

November 19, 2025

URL:

Pharmacologic Treatment of Perinatal Depression

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.17250

Keywords

Pharmacology

Perinatal Depression

Major Depressive Disorder

abuse

depression

PMID (1):

41259042

A review of the treatment of patients with perinatal depression with an emphasis on pharmalogic therapy. James W. Mold, MD, MPH

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Approximately 1 in 7 individuals are affected by perinatal depression, defined as a depressive episode occurring during pregnancy or within 12 months after delivery. Although the diagnostic criteria are similar to those of major depressive disorder, perinatal depression may also include symptoms such as difficulty forming an emotional attachment with the fetus or infant, persistent doubts about parenting abilities, and intrusive thoughts of harm to self or infant.1 Mental health conditions are leading contributors to maternal mortality in the US; among reporting states, the rate of death from perinatal suicide ranges from 4.2 to 21.4 per 100 000 pregnancies.2 Untreated or undertreated perinatal depression increases other maternal risks, including limited engagement in care, impaired relationships, substance use, preeclampsia, and suicide, as well as fetal or neonatal risks, including preterm birth, low birth weight, and disrupted attachment with long-term developmental consequences.3 Individuals from marginalized communities, such as those who are non–English speaking, uninsured, or geographically isolated, experience a higher prevalence of perinatal depression and are at increased risk of underdiagnosis and undertreatment.3

Risk factors for perinatal depression include a personal or family history of depression, abuse, stressful life events, low socioeconomic status, adolescent or single parenthood, and pregnancy complications, such as preterm birth or pregnancy loss. Each factor individually confers only a small increase in risk, making accurate prediction based on clinical factors challenging.4 Therefore, to facilitate early identification and treatment, universal screening during and after pregnancy is recommended. The American College of Obstetricians and Gynecologists (ACOG) recently issued 2 Clinical Practice Guidelines on perinatal mental health, 1 on screening and diagnosis5 and 1 on treatment and management,3 highlighting opportunities for obstetricians to address existing health gaps.

Author/s:

Emily S. Miller, S. Karlene Cunningham, Lauren M. Osborne

Peripheral Neuropathy: A Review

Megan George — Wed, 19 Nov 2025 22:20:00 +0000

Date Added:

November 19, 2025

Journal/Publication:

JAMA

Publication Date:

November 17, 2025

URL:

Peripheral Neuropathy: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi: 10.1001/jama.2025.19400

Keywords

neurology

neuralgia

Peripheral Nerves

MeSH

antidepressive agents

antidepressive agents, tricyclic

Charcot-Marie-Tooth Disease

blood glucose

Cisplatin

diabetic neuropathies

duloxetine hydrochloride

gabapentin

Hypesthesia

hypotension

Hypotension, Orthostatic

Reverse Transcriptase Inhibitors

Venlafaxine Hydrochloride

Peripheral Nerves

neuralgia

A review of the causes and treatment of the symptoms of peripheral neuropathy. Figure 2 and Table 1 may be particularly helpful. James W. Mold, MD, MPH

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Importance Peripheral neuropathy, defined as damage to peripheral nerves, affects approximately 1% of adults worldwide. More than 200 causes of peripheral neuropathy exist, with symptoms ranging in severity from mild toe numbness to debilitating symptoms that can require a wheelchair. Diabetes is the most common cause of neuropathy, affecting approximately 206 million people worldwide.

Observations Peripheral neuropathy is typically length-dependent, which means that symptoms appear in the longest nerve axons (toes) and progress proximally over time. Peripheral neuropathy is typically symmetric and affects sensory axons more than motor axons. Diabetic neuropathy, which is often associated with both sensory symptoms, such as pain, tingling, or numbness; mild weakness; and autonomic symptoms, such as orthostatic hypotension, accounts for more than 50% of peripheral neuropathy in Western populations. Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B12; and monoclonal gammopathies. Up to 27% of adults with neuropathy have no identifiable etiology for their neuropathy after diagnostic testing. Recommended initial testing includes blood glucose (for diabetes), serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation (for monoclonal gammopathies). First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline. Pain often persists despite medical management. At least a 50% reduction in pain was observed in 38% of those with painful diabetic peripheral neuropathy receiving 1200 mg of gabapentin daily. Combination drug therapies for neuropathic pain may provide added benefit. The prognosis of peripheral neuropathy depends on its underlying cause, but complete reversal of nerve damage is uncommon even in cases for which there are available treatments.

Conclusions and Relevance Peripheral neuropathy affects approximately 1% of adults worldwide and may cause sensory, motor, and autonomic symptoms. Diabetes is the most common cause of peripheral neuropathy in Western countries. First-line therapies for neuropathic pain include gabapentin, pregabalin, duloxetine, and amitriptyline.

Author/s:

Michelle L. Mauermann, Nathan P. Staff

Management of Depression in Adults: A Review

Alex Haga — Sun, 16 Jun 2024 18:49:55 +0000

Date Added:

June 16, 2024

Journal/Publication:

JAMA

Publication Date:

June 10, 2024

URL:

Management of Depression in Adults: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.5756

Keywords

depression

Adults

PMID (1):

38856993

MeSH

depression

Depressive Disorder

depressive disorder, major

Bipolar Disorder

antidepressive agents

anxiety disorders

substance-related disorders

Self-Injurious Behavior

A comprehensive review of what we currently know about the treatment of depression in adults. James W. Mold, MD, MPH

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Importance: Approximately 9% of US adults experience major depression each year, with a lifetime prevalence of approximately 17% for men and 30% for women.

Observations: Major depression is defined by depressed mood, loss of interest in activities, and associated psychological and somatic symptoms lasting at least 2 weeks. Evaluation should include structured assessment of severity as well as risk of self-harm, suspected bipolar disorder, psychotic symptoms, substance use, and co-occurring anxiety disorder. First-line treatments include specific psychotherapies and antidepressant medications. A network meta-analysis of randomized clinical trials reported cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all had at least medium-sized effects in symptom improvement over usual care without psychotherapy (standardized mean difference [SMD] ranging from 0.50 [95% CI, 0.20-0.81] to 0.73 [95% CI, 0.52-0.95]). A network meta-analysis of randomized clinical trials reported 21 antidepressant medications all had small- to medium-sized effects in symptom improvement over placebo (SMD ranging from 0.23 [95% CI, 0.19-0.28] for fluoxetine to 0.48 [95% CI, 0.41-0.55] for amitriptyline). Psychotherapy combined with antidepressant medication may be preferred, especially for more severe or chronic depression. A network meta-analysis of randomized clinical trials reported greater symptom improvement with combined treatment than with psychotherapy alone (SMD, 0.30 [95% CI, 0.14-0.45]) or medication alone (SMD, 0.33 [95% CI, 0.20-0.47]). When initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, adding a second antidepressant, or augmenting with a nonantidepressant medication, which have approximately equal likelihood of success based on a network meta-analysis. Collaborative care programs, including systematic follow-up and outcome assessment, improve treatment effectiveness, with 1 meta-analysis reporting significantly greater symptom improvement compared with usual care (SMD, 0.42 [95% CI, 0.23-0.61]).

Conclusions and relevance: Effective first-line depression treatments include specific forms of psychotherapy and more than 20 antidepressant medications. Close monitoring significantly improves the likelihood of treatment success.

Author/s:

Gregory E Simon, Nathalie Moise, David C Mohr

The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Erin Blanchette — Tue, 12 Mar 2024 16:40:40 +0000

Date Added:

March 12, 2024

Journal/Publication:

Annals of Internal Medicine

Publisher:

American College of Physicians

Publication Date:

February 27, 2024

URL:

The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.7326/M23-2757

Keywords

PTSD

veterans

Veterans Health

Department of Veterans Affairs

Department of Defense

antidepressants

PMID (1):

38408360

MeSH

Stress Disorders

stress disorder, post-traumatic

Veterans

antidepressive agents

cannabis

Traumatic

Acute

Cognitive Behavioral Therapy

Recommendations from the Depts of Veterans Affairs and Defense regarding diagnosis and management of PTSD and acute stress disorders. James W. Mold, MD, MPH

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Description: The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. This article summarizes the 2023 clinical practice guideline (CPG) and its development process, focusing on assessments and treatments for which evidence was sufficient to support a recommendation for or against.

Methods: Subject experts from both departments developed 12 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Recommendations were made after consensus was reached; they were based on quality and strength of evidence and informed by other factors, including feasibility and patient perspectives. Once the draft was peer reviewed by an external group of experts and their inputs were incorporated, the final document was completed.

Recommendations: The revised CPG includes 34 recommendations in the following 5 topic areas: assessment and diagnosis, prevention, treatment, treatment of nightmares, and treatment of posttraumatic stress disorder (PTSD) with co-occurring conditions. Six recommendations on PTSD treatment were rated as strong. The CPG recommends use of specific manualized psychotherapies over pharmacotherapy; prolonged exposure, cognitive processing therapy, or eye movement desensitization and reprocessing psychotherapy; paroxetine, sertraline, or venlafaxine; and secure video teleconferencing to deliver recommended psychotherapy when that therapy has been validated for use with video teleconferencing or when other options are unavailable. The CPG also recommends against use of benzodiazepines, cannabis, or cannabis-derived products. Providers are encouraged to use this guideline to support evidence-based, patient-centered care and shared decision making to optimize individuals' health outcomes and quality of life.

Author/s:

Paula P Schnurr, Jessica L Hamblen, Jonathan Wolf, Rachael Coller, Claire Collie, Matthew A Fuller, Paul E Holtzheimer, Ursula Kelly, Ariel J Lang, Kate McGraw, Joshua C Morganstein, Sonya B Norman, Katie Papke, Ismene Petrakis, David Riggs, James A Sall, Brian Shiner, Ilse Wiechers, Marija S Kelber

Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial

Erin Blanchette — Tue, 21 Nov 2023 20:21:34 +0000

Date Added:

November 21, 2023

Journal/Publication:

The Lancet

Publisher:

Elsevier

Publication Date:

November 11, 2023

Issue:

10414

Volume:

402

Pages:

1773-1785

URL:

Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/S0140-6736(23)01523-4

Keywords

amitriptyline

Irritable Bowel Syndrome

primary health care

antidepressive agents

PMID (1):

37858323

MeSH

Irritable Bowel Syndrome* / drug therapy

primary health care

Amitriptyline / adverse effects

antidepressive agents

antidepressive agents, tricyclic

amitriptyline

Irritable Bowel Syndrome

General Practitioners

Low-dose amitriptyline can be an effective and well-tolerated treatment option for patients with irritable bowel syndrome. James W. Mold, MD, MPH

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Background: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting.

Methods: This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants.

Findings: Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication.

Interpretation: To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial.

Funding: National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

Author/s:

Alexander C Ford, Alexandra Wright-Hughes, Sarah L Alderson, Pei-Loo Ow, Matthew J Ridd, Robbie Foy, Gina Bianco, Felicity L Bishop, Matthew Chaddock, Heather Cook, Deborah Cooper, Catherine Fernandez, Elspeth A Guthrie, Suzanne Hartley, Amy Herbert, Daniel Howdon, Delia P Muir, Taposhi Nath, Sonia Newman, Thomas Smith, Christopher A Taylor, Emma J Teasdale, Ruth Thornton, Amanda J Farrin, Hazel A Everitt, ATLANTIS trialists

Maintenance or Discontinuation of Antidepressants in Primary Care

Bethie Seay — Sun, 03 Oct 2021 05:00:00 +0000

Date Added:

October 3, 2021

Journal/Publication:

The New England Journal of Medicine

Publication Date:

September 30, 2021

Type:

Clinical Research Results

DOI (1):

10.1056/NEJMoa2106356

In patients whose depression resolved on antidepressants, discontinuation of the antidepressant is associated with a significantly higher rate of depression reoccurrence vs. maintenance antidepressant therapy over a one year period.

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BACKGROUND
Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting.

METHODS
We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings.

RESULTS
A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group.

CONCLUSIONS
Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)

Author/s:

Lewis, G., Marston, L., Duffy, L., Freemantle, N., Gilbody, S., Hunter, R., Kendrick, T., Kessler, D., Mangin, D., King, M., Lanham, P., Moore, M.

Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

John Bayhi — Fri, 17 Apr 2020 17:32:46 +0000

Date Added:

April 17, 2020

Journal/Publication:

AHRQ Publication No. 20-EHC005-EF

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

April 10, 2020

URL:

Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER224

Keywords

cognitive behavioral therapy

selective serotonin reuptake inhibitors

MeSH

serotonin uptake inhibitors

paroxetine

Depressive Disorder

depressive disorder, major

united states food and drug administration

risk

Inpatients

Confidence Intervals

antidepressive agents

Cognitive Behavioral Therapy

The key findings are listed on the third page (page ii). James W. Mold, MD, MPH

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Background. Depressive disorders can affect long-term mental and physical health functioning among children and adolescents, including increased risk of suicide. Despite access to several nonpharmacological, pharmacological, and combined treatment options for childhood depression, clinicians contend with sparse evidence and are concerned about harms associated with treatment.

Methods. We conducted a systematic review to evaluate the efficacy, comparative effectiveness, and moderators of benefits and harms of available nonpharmacological and pharmacological treatments for children and adolescents with a confirmed diagnosis of a depressive disorder (DD)—major depressive disorder (MDD), persistent depressive disorder (previously termed dysthymia) or DD not otherwise specified. We searched five databases and other sources for evidence available from inception to May 29, 2019, dually screened the results, and analyzed eligible studies.

Results. We included in our analyses data from 60 studies (94 articles) that met our review eligibility criteria. For adolescents (study participants’ ages range from 12 to 18 years) with MDD, cognitive behavioral therapy (CBT), fluoxetine, escitalopram, and combined fluoxetine and CBT may improve depressive symptoms (1 randomized controlled trial [RCT] each, n ranges from 212 to 311); whether the magnitude of improvement is clinically significant is unclear. Among adolescents or children with MDD, CBT plus medications (8–17 years) may be associated with lower rates of relapse (1 RCT [n = 121]). In the same population (6–17 years), selective serotonin reuptake inhibitors (SSRIs) may be associated with improved response (7 RCTs [n = 1,525]; risk difference [RD], 72/1,000 [95% confidence interval (CI), 2 to 24], I2 = 9%) and functional status (5 RCTs [n = 941]; standardized mean difference, 0.16 [95% CI, 0.03 to 0.29]; I2 = 0%). For adolescents or children with any DD (7–18 years), CBT or family therapy may be associated with improvements in symptoms, response, or functional status (1 RCT each, n ranges from 64 to 99). Among children with any DD (7–12 years), family-based interpersonal therapy may be associated with improved symptoms (1 RCT, n = 38). Psychotherapy trials did not report harms. SSRIs may be associated with a higher risk of serious adverse events among adolescents or children with MDD (7–18 years; 9 RCTs [n = 2,206]; RD, 20/1,000 [95% CI, 1 to 440]; I2, 4%) and with a higher risk of withdrawal due to adverse events among adolescents with MDD (12–18 years; 4 RCTs [n = 1,296], RD, 26/1,000 [95% CI, 6 to 45]; I2, 0%). Paroxetine (1 RCT [n = 180]) may be associated with a higher risk of suicidal ideation or behaviors among adolescents with MDD (12–18 years). Evidence was insufficient to judge the risk of suicidal ideation or behavior for other SSRIs for adolescents and children with MDD or other DD (7–18 years) (10 RCTs [n = 2,368]; relative risk, 1.14 [95% CI, 0.89 to 1.45]; I2, 8%). However, this report excluded data on inpatients and those without depressive disorders, whom the Food and Drug Administration included in finding an increased risk of suicidality for all antidepressants across all indications.

Conclusion. Efficacious treatments exist for adolescents with MDD. SSRIs may be associated with increased withdrawal and serious adverse events. No evidence on harms of psychotherapy were identified.

Author/s:

Viswanathan, M, Kennedy, SM, McKeeman, J, Christian, R, Coker-Schwimmer, Cook Middleton, Bann, C, Lux, L, Randolph, Forman-Hoffman, V

Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

Brian Desmarais — Thu, 27 Jun 2019 13:04:17 +0000

Date Added:

June 27, 2019

Journal/Publication:

Journal of the American Medical Association Internal Medicine

Publication Date:

June 24, 2019

URL:

Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2019.0677.

Keywords

MeSH

Muscarinic Antagonists

antipsychotic agents

Middle Aged

Anticonvulsants

Confounding Factors (Epidemiology)

Urinary Bladder

cholinergic antagonists

antidepressive agents

I am only posting this article because your patients may ask about it. The research design isn’t very strong, and the association strengths aren’t terribly impressive. The dementia diagnoses weren’t confirmed, and I can’t tell whether patients were still taking the meds, which we know can cause acute cognitive impairment.. James W. Mold, MD, MPH

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IMPORTANCE:

Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia.

OBJECTIVE:

To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.

DESIGN, SETTING, AND PARTICIPANTS:

This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.

EXPOSURES:

The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).

MAIN OUTCOMES AND MEASURES:

Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.

RESULTS:

Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementiarisk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.

CONCLUSIONS AND RELEVANCE:

Exposure to several types of strong anticholinergic drugs is associated with an increased risk ofdementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.

Author/s:

Coupland, C.A.C., Hill, T., Dening, T., Morriss, R., Moore M., Hippisley-Cox J.

Antidepressant treatment of co-occurring depression and alcohol dependence

Jeffrey Wilson — Mon, 17 Dec 2018 15:08:54 +0000

Date Added:

December 17, 2018

Journal/Publication:

Cochrane Database of Systematic Reviews

Publisher:

Cochrane Library

Publication Date:

April 24, 2018

URL:

Antidepressants for the treatment of people with co-occurring depression and alcohol dependence.

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858.CD008581.pub2

Keywords

depression

alcoholism

antidepressive agents

PMID (1):

29688573

MeSH

depression

antidepressive agents

alcoholism

This meta-analysis included 7 trials (424 participants) found moderate‐quality evidence that, in patients with both alcohol dependency and depression, antidepressants increased the number of participants abstinent from alcohol (RR 1.71, 95% Cl 1.22 to 2.39) and reduced the number of drinks per drinking days (mean difference (MD) ‐1.13 drinks per drinking days, 95% Cl ‐1.79 to ‐0.46).

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BACKGROUND:

Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes.

OBJECTIVES:

To assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol dependence.

SEARCH METHODS:

We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2017. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies.

SELECTION CRITERIA:

Randomized controlled trials and controlled clinical trials comparing antidepressants alone or in association with other drugs or psychosocial interventions (or both) versus placebo, no treatment, and other pharmacological or psychosocial interventions.

DATA COLLECTION AND ANALYSIS:

We used standard methodological procedures as expected by Cochrane.

MAIN RESULTS:

We included 33 studies in the review (2242 participants). Antidepressants were compared to placebo (22 studies), psychotherapy (two studies), other medications (four studies), or other antidepressants (five studies). The mean duration of the trials was 9.9 weeks (range 3 to 26 weeks). Eighteen studies took place in the USA, 12 in Europe, two in Turkey, and one in Australia. The antidepressant included in most of the trials was sertraline; other medications were amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. Eighteen studies were conducted in an outpatient setting, nine in an inpatient setting, and six in both settings. Psychosocial treatment was provided in 18 studies. There was high heterogeneity in the selection of outcomes and the rating systems used for diagnosis and outcome assessment.Comparing antidepressants to placebo, low-quality evidence suggested that antidepressants reduced the severity of depression evaluated with interviewer-rated scales at the end of trial (14 studies, 1074 participants, standardized mean difference (SMD) -0.27, 95% confidence interval (CI) -0.49 to -0.04). However, the difference became non-significant after the exclusion of studies with a high risk of bias (SMD -0.17, 95% CI -0.39 to 0.04). In addition, very low-quality evidence supported the efficacy of antidepressants in increasing the response to the treatment(10 studies, 805 participants, risk ratio (RR) 1.40, 95% Cl 1.08 to 1.82). This result became non-significant after the exclusion of studies at high risk of bias (RR 1.27, 95% CI 0.96 to 1.68). There was no difference for other relevant outcomes such as the difference between baseline and final score, evaluated using interviewer-rated scales (5 studies, 447 participants, SMD 0.15, 95% CI -0.12 to 0.42).Moderate-quality evidence found that antidepressants increased the number of participants abstinent from alcohol during the trial (7 studies, 424 participants, RR 1.71, 95% Cl 1.22 to 2.39) and reduced the number of drinks per drinking days (7 studies, 451 participants, mean difference (MD) -1.13 drinks per drinking days, 95% Cl -1.79 to -0.46). After the exclusion of studies with high risk of bias, the number of abstinent remained higher (RR 1.69, 95% CI 1.18 to 2.43) and the number of drinks per drinking days lower (MD -1.21 number of drinks per drinking days, 95% CI -1.91 to -0.51) among participants who received antidepressants compared to those who received placebo. However, other outcomes such as the rate of abstinent days did not differ between antidepressants and placebo (9 studies, 821 participants, MD 1.34, 95% Cl -1.66 to 4.34; low-quality evidence).Low-quality evidence suggested no differences between antidepressants and placebo in the number of dropouts (17 studies, 1159 participants, RR 0.98, 95% Cl 0.79 to 1.22) and adverse events as withdrawal for medical reasons (10 studies, 947 participants, RR 1.15, 95% Cl 0.65 to 2.04).There were few studies comparing one antidepressant versus another antidepressant or antidepressants versus other interventions, and these had a small sample size and were heterogeneous in terms of the types of interventions that were compared, yielding results that were not informative.

AUTHORS' CONCLUSIONS:

We found low-quality evidence supporting the clinical use of antidepressantsin the treatment of people with co-occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co-occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in peoplewith co-occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest.

Author/s:

Agabio, Roberta, Trogu, Emanuela, Pani, Pier Paolo