Generation Antidepressants Research Articles

Efficacy of Second Generation Antidepressants in Late-Life Depression: A Meta-Analysis of the Evidence

Second-generation antidepressants are commonly used to treat major depression in late-life. This systematic review and meta-analysis was undertaken to assess the evidence for efficacy of second-generation antidepressants in late-life major depression. The Cochrane Library (2006 [3]), MEDLINE (1966 to August 2006), and meeting presentations were searched for trials of second-generation antidepressants (nontricyclics) marketed in the United States. Published and unpublished placebo-controlled randomized clinical trials in outpatients 60 years and older, with nonpsychotic, unipolar major depression were selected. Clinical characteristics and outcomes were extracted. Outcomes were expressed as odds ratios (OR), risk differences, and weighted mean differences. Ten unique trials (four unpublished) with 13 contrasts met selection criteria. Trials were 6-12 weeks duration, and included 2,377 patients who received active drug and 1,788 received placebo. The ORs by meta-analysis for response and remission were 1.40 (95% confidence interval [CI] 1.24-1.57, z = 5.45, N = 13, p <0.001) and 1.27 (CI 1.12-1.44, z = 3.67, N = 13, p <0.001), respectively, with significant heterogeneity for response and remission among the trials. Mean pooled response rates for antidepressant and placebo were 44.4% and 34.7%, respectively. The OR for response was significantly higher in the 10-12 week trials (OR = 1.73, CI 1.42-2.09, z = 5.51, N = 5, p <0.001) than the 6-8 week trials (OR = 1.22, CI 1.05-1.42, z = 2.60, N = 8, p = 0.01). ORs for discontinuation for any reason and for adverse events were significantly higher with drugs than with placebo. Antidepressants are more effective than placebo in elderly depressed subjects although effects are modest and vary. Identification of the characteristics of responders and nonresponders will be crucial to improving treatment outcomes.

Efficacy of Second Generation Antidepressants in Late-Life Depression: A Meta-Analysis of the Evidence

Objective Second-generation antidepressants are commonly used to treat major depression in late-life. This systematic review and meta-analysis was undertaken to assess the evidence for efficacy of second-generation antidepressants in late-life major depression. Methods The Cochrane Library (2006 [3]), MEDLINE (1966 to August 2006), and meeting presentations were searched for trials of second-generation antidepressants (nontricyclics) marketed in the United States. Published and unpublished placebo-controlled randomized clinical trials in outpatients 60 years and older, with nonpsychotic, unipolar major depression were selected. Clinical characteristics and outcomes were extracted. Outcomes were expressed as odds ratios (OR), risk differences, and weighted mean differences. Results Ten unique trials (four unpublished) with 13 contrasts met selection criteria. Trials were 6–12 weeks duration, and included 2,377 patients who received active drug and 1,788 received placebo. The ORs by meta-analysis for response and remission were 1.40 (95% confidence interval [CI] 1.24–1.57, z = 5.45, N = 13, p <0.001) and 1.27 (CI 1.12–1.44, z = 3.67, N = 13, p <0.001), respectively, with significant heterogeneity for response and remission among the trials. Mean pooled response rates for antidepressant and placebo were 44.4% and 34.7%, respectively. The OR for response was significantly higher in the 10–12 week trials (OR = 1.73, CI 1.42–2.09, z = 5.51, N = 5, p <0.001) than the 6–8 week trials (OR = 1.22, CI 1.05–1.42, z = 2.60, N = 8, p = 0.01). ORs for discontinuation for any reason and for adverse events were significantly higher with drugs than with placebo. Conclusions Antidepressants are more effective than placebo in elderly depressed subjects although effects are modest and vary. Identification of the characteristics of responders and nonresponders will be crucial to improving treatment outcomes. Second-generation antidepressants are commonly used to treat major depression in late-life. This systematic review and meta-analysis was undertaken to assess the evidence for efficacy of second-generation antidepressants in late-life major depression. The Cochrane Library (2006 [3]), MEDLINE (1966 to August 2006), and meeting presentations were searched for trials of second-generation antidepressants (nontricyclics) marketed in the United States. Published and unpublished placebo-controlled randomized clinical trials in outpatients 60 years and older, with nonpsychotic, unipolar major depression were selected. Clinical characteristics and outcomes were extracted. Outcomes were expressed as odds ratios (OR), risk differences, and weighted mean differences. Ten unique trials (four unpublished) with 13 contrasts met selection criteria. Trials were 6–12 weeks duration, and included 2,377 patients who received active drug and 1,788 received placebo. The ORs by meta-analysis for response and remission were 1.40 (95% confidence interval [CI] 1.24–1.57, z = 5.45, N = 13, p <0.001) and 1.27 (CI 1.12–1.44, z = 3.67, N = 13, p <0.001), respectively, with significant heterogeneity for response and remission among the trials. Mean pooled response rates for antidepressant and placebo were 44.4% and 34.7%, respectively. The OR for response was significantly higher in the 10–12 week trials (OR = 1.73, CI 1.42–2.09, z = 5.51, N = 5, p <0.001) than the 6–8 week trials (OR = 1.22, CI 1.05–1.42, z = 2.60, N = 8, p = 0.01). ORs for discontinuation for any reason and for adverse events were significantly higher with drugs than with placebo. Antidepressants are more effective than placebo in elderly depressed subjects although effects are modest and vary. Identification of the characteristics of responders and nonresponders will be crucial to improving treatment outcomes.

Studies toward the discovery of the next generation of antidepressants. Part 6: Dual 5-HT 1A receptor and serotonin transporter affinity within a class of arylpiperazinyl-cyclohexyl indole derivatives

Based on the previously reported discovery lead, 3-( cis-4-(4-(1 H-indol-4-yl)piperazin-1-yl)cyclohexyl)-5-fluoro-1 H-indole ( 2), a series of related arylpiperazin-4-yl-cyclohexyl indole analogs were synthesized then evaluated as 5-HT transporter inhibitors and 5-HT 1A receptor antagonists. The investigation of the structure–activity relationships revealed the optimal pharmacophoric elements required for activities in this series. The best example from this study, 5-(piperazin-1-yl)quinoline analog ( trans- 20), exhibited equal binding affinities at 5-HT transporter ( K i = 4.9 nM), 5-HT 1A receptor ( K i = 6.2 nM) and functioned as a 5-HT 1A receptor antagonist.

Restless legs syndrome as side effect of second generation antidepressants

Although of clinical interest, the question is still not fully answered whether antidepressants (AD) can cause or exacerbate restless legs syndrome (RLS). The literature provides contradictory information. This study addresses this problem for the class of second generation AD. In four neurological offices, all patients treated for the first time with an AD were prospectively observed with regard to the question of whether RLS occurred or pre-existing RLS worsened as a result of the medication. Because initial treatment in the participating offices is mainly executed with “modern” selective AD, the study was restricted to these drugs (fluoxetine, paroxetine, citalopram, sertraline, escitalopram, venlafaxine, duloxetine, reboxetine, and mirtazapine). In 9% of patients, RLS was recorded as a side effect related to the administration of AD. The frequency of this side effect varied among the drugs. The problem is most pronounced with mirtazapine provoking or deteriorating RLS in 28% of patients. By contrast, no case occurred during use of reboxetine. As for the other AD, the rate of newly occurred and deteriorated RLS, ranged from 5% to 10%. Typically, RLS occurred during the initial days of treatment.

Fatal intoxication with milnacipran

The antidepressant milnacipran is a double serotonin/noradrenalin reuptake inhibitor. The low reported incidence of intoxication indicates excellent tolerance in comparison with tricyclic and second generation antidepressants. We report a fatal intoxication associating milnacipran, at blood levels (femoral = 21.5 mg/l, cardiac = 20 mg/l) 40-fold higher than the usual treatment concentration, and six other molecules (fluoxetine, norfluoxetine, sertraline, cyamemazine, nordazepam and oxazepam) at therapeutic levels. To the best of our knowledge, this is the first reported fatal intoxication involving milnacipran.

Treatment of Rapid-Cycling Bipolar Disorder: Are Antidepressants Mood Destabilizers?

Treatment of Rapid-Cycling Bipolar Disorder: Are Antidepressants Mood Destabilizers?

Relevant Issues in the Monitoring and the Toxicology of Antidepressants

This review provides specific information concerning the interpretation and usefulness of antidepressant drug monitoring. Fifteen antidepressants (ADs) were selected based on their importance in the 7 major markets (Japan, USA, France, United Kingdom, Italy, Spain, Germany) according to the Cognos Plus Study #11. Literature data were reviewed concerning monitoring of the tricyclic ADs amitriptyline, clomipramine, imipramine, and new generation antidepressants such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, mianserin, mirtazapine, bupropion, and milnacipran. In addition, St.-John's Wort was added as this natural antidepressant is very popular in Europe. The objectives of therapeutic drug monitoring (TDM) for old and new generation ADs differs, as older ADs have narrow therapeutic windows with higher risks of severe drug interactions, while the new ADs have a wide therapeutic range, but an unclear plasma concentration-effect relationship. Therefore, the purpose of TDM for new-generation ADs leads more to the monitoring of patient compliance and special patient groups such as the elderly, patients with liver and kidney impairment, patients with poor metabolism by CYP 450 and comedication with inhibitors and inducers of those enzymes.

Differences in Medication Adherence and Healthcare Resource Utilization Patterns

Given the number of antidepressants available and their rising costs, healthcare payers have initiated restrictive reimbursement policies for newer antidepressants, without consideration for differences in their effectiveness or tolerability. The objective of this study was to comprehensively compare medication adherence rates and associated healthcare utilization costs for patients using later-generation versus earlier-generation antidepressants in a managed care setting. Antidepressants launched after 2002 were deemed third-generation antidepressants, while antidepressants available prior to 2002 were deemed first-generation (TCAs and MAOIs) and second-generation (serotonin and noradrenaline [norepinephrine]-dopamine reuptake inhibitors). Retrospective database analysis using medical and pharmacy data from over 75 managed care plans covering 55 million lives. All patients receiving an antidepressant between 1 January 2002 and 30 September 2004 were identified. The index date for patients was the date of their first antidepressant prescription within this time period. Patients had to (i) have a diagnosis of depression or anxiety disorder, or depression and anxiety disorder within 6 months prior to or 30 days after their index prescription; (ii) be at least 18 years of age, without having taken antidepressant therapy for 6 months prior to their index date; and (iii) be continuously eligible for 6 months prior to their index date and during their 6-month follow-up period. Patients were excluded if they had a diagnosis of psychosis-related disease, Alzheimer's or Parkinson's disease, or were initiated on psychosis-related medications. INTERVENTION/MAIN OUTCOME MEASURE: Patients meeting selection criteria were followed for 6 months to assess rates of antidepressant adherence, therapy change rates and medical healthcare costs. A total of 266 665 patients met the study criteria. Approximately 66% were female, with a mean age of 39 years. About 63% had a diagnosis of depression, 31% had an anxiety disorder diagnosis and 6% had diagnoses for both an anxiety disorder and depression. Therapy change: Therapy change within 6 months occurred in 18% of patients receiving third-generation agents compared with 21% and 40% for second- and first-generation agents, respectively. The odds of a therapy change were significantly lower with third-generation antidepressants compared with both older agent cohorts. Adherence: Of patients receiving third-generation antidepressants, 33.6% were adherent compared with 29.3% and 12.4% of patients receiving second- and first-generation antidepressants, respectively. Newer agents also had better adherence rates across all diagnostic cohorts. After adjusting for baseline differences, the odds of being adherent to therapy were significantly lower for those taking second- and first-generation agents versus newer antidepressants. Among the newer agents, the proportion of patients adherent to their therapy was: venlafaxine extended release 38%, paroxetine controlled release (CR) 35%, escitalopram 34%, duloxetine 32% and bupropion extended release (XL) 31%. Healthcare utilization: Of the patients taking older antidepressants, 13% (second generation) and 21% (first generation) were hospitalized at least once for any reason compared with 12% of patients taking newer agents. Overall, the odds of all-cause hospitalization within 6 months of therapy initiation were significantly higher for patients taking older antidepressants. Among the newer agents, hospitalization rates ranged from 15.9% for duloxetine to 12.5% for paroxetine CR and bupropion XL. The unadjusted 6-month total medical costs (not including pharmacy costs) per patient were $US 3514 for second-generation, $US 5744 for first-generation and $US 3284 for newer antidepressants. After controlling for baseline differences, patients receiving second- and first-generation antidepressants incurred 12% and 44% higher costs, respectively. The unadjusted 6-month medical costs for the newer agents ranged from $US 2715 for paroxetine CR to $US 6042 for duloxetine. The results of this study provide essential information for healthcare decision makers about the potential advantages of newer generation antidepressants versus older generation antidepressants, as well as the differences between the specific newer agents, with respect to improved rates of adherence and therapy change, reduced hospitalizations and healthcare costs.

Comparison of electron and chemical ionization modes by validation of a quantitative gas chromatographic–mass spectrometric assay of new generation antidepressants and their active metabolites in plasma

A gas chromatographic–mass spectrometric method (GC–MS) for the simultaneous determination of the ‘new’ antidepressants (mirtazapine, viloxazine, venlafaxine, trazodone, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine) and their active metabolites (desmethylmirtazapine, O-desmethylvenlafaxine, m-chlorophenylpiperazine, desmethylcitalopram, didesmethylcitalopram, desmethylmianserin, desmethylfluoxetine, desmethylsertraline, desmethylmaprotiline) in plasma using different ionization modes was developed and validated. Sample preparation consisted of a strong cation exchange mechanism and derivatisation with heptafluorobutyrylimidazole. The GC separation was performed in 24.8 min. Identification and quantification were based on selected ion monitoring in electron (EI) and chemical ionization (CI) modes. Calibration by linear and quadratic regression for electron and chemical ionization, respectively, utilized deuterated internal standards and a weighing factor 1/ x 2. Limits of quantitation were established between 5 and 12.5 ng/ml in EI and positive ionization CI (PICI), and 1 and 6.25 ng/ml in negative ionization CI (NICI). During validation stability, sensitivity, precision, accuracy, recovery, and selectivity were evaluated for each ionization mode and were demonstrated to be acceptable for most compounds. While it is clear that not all compounds can be quantitated either due to chromatographic (trazodone) or derivatisation problems ( O-desmethylvenlafaxine), this method can quantitate most new antidepressants (ADs) in the therapeutic range using EI. PICI and NICI lead to higher selectivity. Moreover, NICI is of interest for small sample volumes and high sensitivity requirements. This paper draws the attention to the pros and cons of the different ionization modes in the GC–MS analysis of these antidepressants in plasma.

Enhanced selective serotonin re-uptake inhibitors as antidepressants: 2004 – 2006

Depression is a major psychiatric disorder. It affects millions of people worldwide and inflicts tremendous economic burden on societies. The advent of selective serotonin re-uptake inhibitors as antidepressants has been a revolutionary advance in the treatment of depression and related disorders. However, selective serotonin re-uptake inhibitors are also associated with several undesirable properties, such as delayed onset of action, low response rate and side effects. The present search for a newer generation of antidepressants is focused on overcoming these issues. The patent literature covered in this review, during 2004 – 2006, illustrates several strategies employed by the pharmaceutical industry in the development of enhanced serotonin re-uptake inhibitors. Encouraged by the success of venlafaxine and duloxetine, several companies have pursued dual-acting serotonin and noradrenaline re-uptake inhibitors as drug candidates for depression treatment. Molecules with combined serotonin re-uptake inhibitor and 5-HT autoreceptor (5-HT1A and/or 5-HT1B) antagonist properties are being developed. In particular, recent research suggests that serotonin 5-HT1B antagonists alone or combined with selective serotonin re-uptake inhibitors might hold unique promise as efficacious antidepressants. Finally, efforts are underway to formulate new drug candidates with both serotonin re-uptake inhibitor and neurokinin 1 (NK1) antagonist activities. Despite mixed results from clinical trials with several NK1 antagonists, effective therapeutic agents for depression may still emerge from compounds with combined serotonin reuptake inhibitor/NK1 antagonist properties.

Adherence to Antidepressant Treatment Among Privately Insured Patients Diagnosed With Depression

Antidepressants are effective in treatment of depression, but poor adherence to medication is a major obstacle to effective care. We sought to describe patient and provider level factors associated with treatment adherence. This was a retrospective, observational study using medical and pharmacy claims from a large health plan, for services provided between January 2003 and January 2005. We studied a total of 4312 subjects ages 18 or older who were continuously enrolled in the health plan with a new episode of major depression and who initiated antidepressant treatment. Treatment adherence was measured by using pharmacy refill records during the first 16 weeks (acute phase) and the 17-33 weeks after initiation of antidepressant therapy (continuation phase). Measures were based on Health Plan Employer Data and Information Set (HEDIS) quality measures for outpatient depression care. Fifty-one percent of patients were adherent through the acute phase; of those, 42% remained adherent in the continuation phase. Receipt of follow-up care from a psychiatrist and higher general pharmacy utilization (excluding psychotropics) were associated with better adherence in both phases. Younger age, comorbid alcohol or other substance abuse, comorbid cardiovascular/metabolic conditions, use of older generation antidepressants, and residence in lower-income neighborhoods were associated with lower acute-phase adherence. Continuation-phase adherence was lower for HMO participants than for others. In an insured population, many patients fall short of adherence to guideline recommended therapy for depression. Information from existing administrative data can be used to predict patients at highest risk of nonadherence, such as those with substance abuse, and to target interventions.

Antidepressants and youth: Healing or harmful?

A series of drug innovations that began in 1987, including the introduction of several selective serotonin reuptake inhibitors (SSRIs), has led to a tremendous growth in the use of antidepressants in the United States. This growth, however, has been accompanied by a growing concern about the risks of prescribing antidepressants, particularly to children. Indeed, research linking the use of antidepressant drugs to an increased risk of suicidal behaviors in youth motivated the US Food and Drug Administration to direct antidepressant drug manufacturers to include warning labels about the potential dangers. This paper examines the relationship between antidepressants and suicide among youth in the USA. Using state-level data on youth suicides and age-specific prescriptions for antidepressants, we find no relationships between suicides for adolescents aged 15–19 and prescriptions for SSRIs/serotonin–norepinephrine reuptake inhibitors or tricyclic and tetracyclic antidepressants. In contrast, we find that newer generation antidepressants are associated with lower numbers of suicides for this age group. For younger children aged 10–14, we find no relationship with suicides for any type of antidepressant.

FDA Panel Seeks to Balance Risks in Warnings for Antidepressants

NEWER GENERATION ANTIDEPRESsants should carry a broader warning of an increased risk of suicidal thoughts and behaviors in not only children and adolescents, but also young adults, recommended a US Food andDrugAdministration(FDA)advisory committee after considering new data fromtheagency.Butinanunprecedented step,thepanelalsorecommendedthatthe warningsincludeinformationonthebenefitsof treatingdepressionandtheriskof suicideassociatedwithuntreateddepression, based on emerging data that warnings about potential adverse effects of medicationsmayleadtoundertreatment and subsequent suicides. ThecommitteemetDecember13and voted 6 to 2 in favor of extending the existingblackboxwarnings,althoughmembers alsoagreed that thewarningshould address thebenefitsof treatmentand the risksassociatedwithdecliningtreatment, said Daniel S. Pine, MD, acting chair of thecommitteeandchiefofchildandadolescent researchat theNational Institute ofMentalHealth.TheFDAhasyet todecidewhether toaccept therecommendations, but typically the agency does follow its committees’ advice.

5-HT7 Receptor Antagonists as a New Class of Antidepressants

It is now admitted that major depression is associated with monoaminergic dysfunctions as well as with functional brain plasticity impairments. Despite the wide variety of medications available to treat such a syndrome, two foremost problems still remain unresolved: one-third of patients do not respond to any treatment and there is an unwanted 2-4 week delay in the onset of therapeutic action of all available antidepressant drugs. These issues draw attention to the need and urgency to develop more efficacious treatments and to accelerate the antidepressant response. The combination of an atypical antipsychotic, known to be a potent 5-HT(7) receptor antagonist, with an antidepressant has been recently proposed as an alternative therapy. Hence, blockade of 5-HT(7) receptors might represent a key determinant for this hastening strategy. This review summarizes recent data that put emphasis on the putative antidepressant properties of selective 5-HT(7) receptor antagonists. The use of such ligands seems very promising to elaborate novel generations of antidepressants that surpass the efficacy and onset of action limitations of existing antidepressants.

Trends in Suicide Risk Associated With Hospitalized Psychiatric Illness

In light of the consistent reduction in suicide rate during the past 20 years in Denmark, this study aims to investigate trends in suicide risk associated with hospitalized psychiatric illness and to explore differences in the changes with regard to clinical phases of illness, sex, age, and diagnosis. This population-based study includes all of 21,169 suicides in Denmark during the years 1981 through 1997 and 423,128 controls matched for sex, age, and time (using a nested case-control design). Personal data on psychiatric history and socioeconomic status were retrieved from Danish longitudinal registers. Data were analyzed using conditional logistic regression. This study shows that the reduction in suicide rate is generally faster among individuals with a history of psychiatric admission than among individuals without such a history. However, this substantial reduction is mainly accounted for by the reduction among patients who had been discharged from psychiatric hospitals for more than 1 year. For patients who had been discharged from hospitals within 1 year, the reduction is similar to that of the general population; while for patients hospitalized for treatment at the time of suicide or the index date, the reduction in suicide rate is relatively slower. Such trends hold for all diagnostic groups. Further analyses stratified by age indicate that the faster reduction in suicide rate associated with history of hospitalized psychiatric illness is more pronounced among patients aged 36 years and older. The reduction in suicide rate is substantial for patients who have been discharged from psychiatric hospitals for more than 1 year and for middle-aged and older patients. Recent improvement in psychiatric care and treatment and promotion of new generation antidepressants may contribute to these changes.

Clinical characteristics and pain management among patients with painful peripheral neuropathic disorders in general practice settings

Alleviating chronic pain is a global healthcare priority. Understanding the medical profile and current treatment patterns in patients with painful neuropathic disorders (PNDs) is crucial to the development of effective pain management strategies. Thus, our objective was to describe the demographic and clinical characteristics of persons with PNDs and their use of pain medications. Using the general practice research database, we categorized PNDs in two ways: Pure PNDs (which include diabetic neuropathy, postherpetic neuralgia, etc.; N = 16,690) and Mixed PNDs (which include back/neck pain with neuropathic involvement; N = 14,309). On average, PND patients were 55 years old (Pure, 55.4 [SD = 16.9] years; Mixed, 54.3 [SD = 16.4] years). Over a third had other chronic pain-related (Pure, 37.5%; Mixed, 37.1%) and nearly a quarter had non-pain related (Pure, 28.1%; Mixed, 24.1%) comorbidities. Use of medications with clinically demonstrated efficacy in PNDs was higher among patients with Pure PNDs (tricyclic antidepressants [Pure, 16.6%; Mixed, 10.1%]; 2nd generation antidepressants [Pure, 11.0%; Mixed, 9.7%]; and antiepileptics [Pure, 12.2%; Mixed, 2.6%]), whereas use of NSAIDs (Pure, 43.1%; Mixed, 65.2%) and opioids (Pure, 8.5%; Mixed, 14.3%) was higher among patients with Mixed PNDs. Average daily doses of select neuropathic pain-related medications among PND patients (Pure and Mixed) were lower than those recommended for neuropathic pain. Among both Pure and Mixed PND patients, use and doses of evidenced-based neuropathic pain-related medications was low, and lower than the use of NSAIDs (a medication class with no proven efficacy for PNDs) in each group, suggesting possible sub-optimal neuropathic pain management among these patients.

Long-term effects of antidepressants on cognition in patients with Alzheimer's disease

Approximately 25-40% of patients with Alzheimer's disease (AD) may develop depression. Antidepressants are typically used to treat depression in this population. However, their effect on cognition has been rarely studied and the results are conflicting. In addition, the long-term effects of antidepressants on cognition have not been studied. Therefore, the objective of the study was to evaluate the effects on cognition in patients with AD treated with antidepressants for at least 9 months. Data on antidepressant use over a minimum period of 9 months were retrospectively collected for patients with AD receiving cholinesterase inhibitors. Data on cognition were analyzed to compare those taking antidepressant therapy and those not receiving antidepressants. Ninety-nine of 210 patients met our inclusion criteria. Fifty-eight patients were prescribed an antidepressant (e.g. selective serotonin reuptake inhibitors (SSRIs), newer generation antidepressants). Sertraline (mean dose: 82 mg/day) and citalopram (mean dose: 35 mg/day) were the most commonly prescribed antidepressants. The baseline mean Mini Mental State Examination (MMSE) score was 16.32 with an average annual rate of cognitive decline of 2.55 for patients receiving antidepressants compared with 16.59 (P = NS) and 2.27 (P = NS) for those not taking antidepressants. Our small sample data indicate no differences in baseline MMSE scores and cognitive decline between the two groups, suggesting antidepressants did not contribute significantly to cognitive decline over a utilization period of at least 9 months.

Latest review supports warnings about safety of newer generation antidepressants in young people

Latest review supports warnings about safety of newer generation antidepressants in young people

The Next Generation of antidepressants

Deletion of the background potassium channel TREK-1 increases the activity of serotonergic neurons and blocks behaviors associated with depression.

The cost of mood disorders

Mood disorders place substantial clinical, social and economic burdens on individuals with the disorders, as well as on their families and wider society. At the same time, the scarcity of healthcare resources necessitates the efficiency of alternative treatments to be examined. Economic evaluations of the seemingly expensive SSRIs have tended to suggest that they are cost-effective compared with tricyclics due to better clinical outcomes and reduced hospitalizations. However, a third generation of antidepressants may bring new cost concerns. The high cost of psychological therapies may mean that they are only cost-effective for particular sub-groups of patients, as suggested by recent NICE guidelines.