Depression treatment patterns among adults with chronic obstructive pulmonary disease and depression

Objective: To estimate rates and patterns of depression treatment among adults with chronic obstructive pulmonary disease (COPD) and depression.

Methods: We used a retrospective, cross-sectional study design, pooling data from 2010 and 2012 Medical Expenditure Panel Survey (MEPS). The study sample consisted of 527 individuals aged 21 years or older, diagnosed with COPD and depression. Depression treatment was grouped into three categories based on those who received: (1) neither antidepressant nor psychotherapy; (2) antidepressants only; and (3) psychotherapy combined with antidepressants (combination therapy). We conducted chi-squared tests and multinomial logistic regressions to examine factors (demographic, socio-economic characteristics, healthcare access, health status, and personal health practices) associated with depression treatment among adults with COPD and depression.

Key findings: The mean age of the study sample was 55.96 years (SD?=?13.36). Overall, 18.8% of the sample adults did not report any use of antidepressants or psychotherapy, 58.3% reported antidepressants use only and 23% reported using combination therapy. Females (adjusted odds ratio [AOR]?=?1.89, 95% CI?=?1.02, 3.55), older adults (≥65 years: AOR?=?3.69, 95% CI?=?1.62, 8.41), adults with fair/poor physical health status (AOR?=?3.32, 95% CI?=?1.29, 8.56) and those suffering from anxiety (AOR?=?1.94, 95% CI?=?1.09, 3.46) were more likely to receive antidepressant treatment. Older adults (AOR =2.94, 95% CI =?1.05, 8.22), those who were never married (AOR?=?3.17, 95% CI?=?1.18, 8.56), suffered from anxiety (AOR =6.01, 95% CI?=?3.11, 11.61) and current smokers (AOR?=?2.29, 95% CI?=?1.05, 4.98) were more likely to receive combination therapy. Whereas, adults who were uninsured (AOR?=?0.21, 95% CI?=?0.05, 0.86) and did not lacked regular physical activity (AOR?=?0.33, 95% CI?=?0.16, 0.67) were less likely to receive combination therapy. A key limitation of our study is that we could not control for the severity of depression or COPD which may have influenced depression treatment.

Conclusion: Efforts to improve depression care among adults with co-occurring COPD and depression may need to be tailored for different subgroups.     

Pharmacotherapy of major depressive disorder in adolescents

Importance of the field: At any one time, major depressive disorder (MDD) affects 4 – 6% of adolescents. When untreated, MDD leads to a high immediate and subsequent suicide risk, long-term chronicity and a poor psychosocial outcome. Whereas psychotherapy can be effective in mild depression, it seems to be less effective in moderate and severe depression. However, although the use of antidepressants increased markedly during the 1990s, in recent years it has decreased as a result of concerns regarding the emergence of suicidality during antidepressant treatment.

Areas covered in this review: Are antidepressants truly effective? What is the relationship between different treatments for depression – psychotherapy and pharmacotherapy – alone or in combination? Can antidepressants increase the risk of suicide in some adolescents? Can antidepressants reduce suicide risk in suicidal adolescents?

What the reader will gain: There is evidence that selective serotonin reuptake inhibitors (SSRIs) can improve adolescent depression better than placebo, although the magnitude of the antidepressant effect is ‘small to moderate’, because of a high placebo response. The SSRI with the best rate of response compared to placebo is fluoxetine. The increased risk of suicidality in adolescents, compared to adults, is weak but consistent across most studies. However, epidemiological studies do not support a relationship between use of antidepressants and suicide rate.

Take home message: A cautious and well-monitored use of antidepressant medications is a first-line treatment option in adolescents with moderate to severe depression. Low rates of remission with current treatment strategies indicate that further research in both psychotherapy and pharmacotherapy is warranted.     

The association of race, comorbid anxiety, and antidepressant adherence among Medicaid enrollees with major depressive disorder

BackgroundDepressed patients often have comorbid anxiety. African-Americans with depression are less likely to adhere to antidepressant treatment. Knowledge of the association between race, comorbid anxiety, and adherence among Medicaid enrollees with depression is limited.ObjectiveThe objective of this study was to evaluate the association of race, comorbid anxiety, and antidepressant adherence, and persistence among Medicaid enrollees with major depressive disorder (MDD).MethodsThe MarketScan^® Multi-State Medicaid Database (Thomson Reuters, Ann Arbor, MI) was used in this retrospective cross-sectional study. Medicaid enrollees aged between 18 and 64 years, with MDD but without bipolar disorders, and with a newly initiated antidepressant between January 1, 2004 and December 31, 2006 were identified. An index date was assigned corresponding to the newly initiated antidepressant. Patients having claims for any antidepressant refills during the 12 months before the index date were excluded. Eligible patients were then followed-up for 12 months after the index date. Adherence was measured by a modified medication possession ratio. Adherence was evaluated using multivariate logistic regression. Persistence was assessed based on treatment discontinuation and examined by Kaplan-Meier survival curves and Cox-propositional hazard regression models.ResultsA total of 3083 Medicaid patients with MDD were included. Approximately, 25% of patients had comorbid anxiety. The odds of adhering to antidepressants were 40% lower among African-Americans than Caucasians, adjusting for covariates (AOR [adjust odds ratio] = 0.60; 95% confidence interval [CI] = 0.51-0.72, P < .001). MDD patients with comorbid anxiety were more likely to adhere to antidepressants than patients with MDD alone (AOR = 1.55, 95% CI = 1.27-1.90, P < .001). African-Americans had a higher hazard of not persistently taking antidepressants (hazard ratio = 1.47, 95% CI = 1.30-1.65, P < .001). The interaction between race and comorbid anxiety was not associated with adherence or persistence.ConclusionsAmong Medicaid enrollees with MDD, race and comorbid anxiety disorders are significantly associated with antidepressant adherence and persistence. Physicians need to recognize comorbid anxiety and race as 2 important determinants of antidepressant use behaviors when they encounter Medicaid patients with MDD.     

Impact of adherence to antidepressants on healthcare outcomes and costs among patients with type 2 diabetes and comorbid major depressive disorder

Objective: To evaluate the association between adherence to antidepressants and an effect on clinical outcomes and healthcare costs in patients with major depressive disorder (MDD) and comorbid type 2 diabetes (T2D).

Methods: This retrospective study used MarketScan claims data from January 2012 to March 2014. Study entry was the first claim for an antidepressant and a diagnosis code for MDD and T2D in the prior 6 months. Adherence and persistence with antidepressant therapy in the first 180 days were defined as medication possession ratio (MPR)?≥?80% and length of therapy (LOT), with no treatment gap of >15 days, respectively. T2D control (HbA1c <7%), oral diabetes medication adherence, and healthcare costs were measured in the 12 month post-index period. The impact of antidepressant adherence and persistence on outcomes was assessed using multivariable analyses.

Results: Among the 1361 patients included, the mean age was 59 years and 55% were women. About one-third of the patients were adherent (35.9%, mean MPR?=?40%), persistent (32.0%, average LOT?=?100 days), and adherent/persistent (31.2%) on antidepressants. Being adherent, persistent, or adherent/persistent to antidepressants was associated with a two-fold improvement in adherence to oral diabetes medications. Of those with HbA1c data (n?=?121), adherence or adherence/persistence to antidepressants was associated with patients being five times more likely to have T2D control (odds ratio [OR]: 4.95; 95% confidence interval [CI]: 1.39, 17.59, p?=?.0134). Comparison between antidepressant-persistent and non-persistent patients was not significant. Mean difference in adjusted all-cause annual costs showed lower costs among antidepressant-adherent and adherent/persistent patients (adherent: -$350, 95% CI: -$462, -$247; adherent/persistent: -$1165; 95% CI: -$1280, -$1060).

Conclusions: Patients with better antidepressant adherence and adherence/persistence demonstrated better HbA1c control, with lower all-cause total and medical costs. Adherence, persistence, or adherence/persistence to antidepressants was associated with improved adherence to oral diabetes medications.     

The effects of chronic norepinephrine transporter inactivation on seizure susceptibility in mice.

Epilepsy and depression are comorbid disorders, but the mechanisms underlying their relationship have not been identified. Traditionally, many antidepressants have been thought to increase seizure incidence, although this remains controversial, and it is unclear which medications should be used to treat individuals suffering from both epilepsy and depression. Since the neurotransmitter norepinephrine (NE) has both antidepressant and anticonvulsant properties, we speculated that NE transporter (NET) inhibitor antidepressants might be therapeutic candidates for comorbid individuals. To test this idea, we assessed the effects of chronic administration (via osmotic minipump) of the selective NET inhibitor reboxetine on flurothyl-induced seizures in mice. We found that reboxetine had both proconvulsant and anticonvulsant properties; it lowered both seizure threshold and maximal seizure severity. NET knockout (NET KO) mice essentially phenocopied the effects of reboxetine on flurothyl-induced seizures, and the trends were extended to pentylenetetrazole and maximal electroshock seizures (MES). Furthermore, reboxetine had no further effect in NET KO mice, demonstrating the specificity of reboxetine for the NET. We next tested the chronic and acute effects of other classes of antidepressants (desipramine, imipramine, sertraline, bupropion, and venlafaxine) on seizure susceptibility. Only venlafaxine was devoid of proconvulsant activity, and retained some anticonvulsant activity. These results suggest that chronic antidepressant drug treatment has both proconvulsant and anticonvulsant effects, and that venlafaxine is a good candidate for the treatment of epilepsy and depression comorbidity.     

Psychiatry should not become hostage to placebo: An alternative interpretation of antidepressant–placebo differences in the treatment response in depression

BackgroundIt is widely believed that in randomized controlled trials of antidepressants the difference between drug and placebo response rates is rather small (around 20%), leading to a common perception that antidepressants have limited efficacy.AimThe aim of the present paper was to present an alternative calculation and interpretation of antidepressant–placebo difference in the treatment response to antidepressant in drug trials which may shed a new light on the efficacy of antidepressants.IssuesWe have previously highlighted several controversial points concerning the calculation of antidepressant and placebo response rates in randomised controlled trials, which may influence views concerning the efficacy of drugs, and demonstrated several factors which may lead to overestimation of the placebo effect and underestimation of antidepressant efficacy. The traditional interpretation of antidepressant–placebo difference in randomized controlled trials on major depression has been also challenged previously from at least five points of view but all leading to a conclusion that currently prevailing opinions concerning relative placebo and antidepressant response rates overestimate placebo response, and thereby underestimate efficacy of antidepressant drugs. In our present paper we propose another method for calculating placebo and antidepressant response rates which may shed new light on an overlooked aspect of the efficacy of these drugs.ConclusionsWe contend that opinions on the effectiveness of antidepressants should be reconsidered, and comparisons with placebo should be more carefully applied. Interpretation of the placebo response is of crucial importance for establishing the efficacy of antidepressive medications, and psychiatry should not become the hostage of placebo.     

Achieving abstinence by treating depression in the presence of substance-use disorders

BACKGROUND: Antidepressants can have an effect on depressive symptoms in participants with comorbid drug or alcohol dependence and mood disorder, but their effect on drug use is not known. It has been suggested that adding psychosocial intervention to antidepressants would enhance the effect on drug use. METHOD: A meta-analysis was conducted on trials of antidepressants for this comorbidity with and without psychosocial treatment. RESULTS: Studies using cognitive-behavioural therapy (CBT) found no medication effect, whereas with no intervention, medication was superior to placebo, manualised counselling falling in between. CONCLUSION: There is no evidence that antidepressant medication is more efficacious in reducing drug use with conjunctive psychosocial treatment. Antidepressant medication and psychotherapy may both be useful in the treatment of substance-dependent depressed patients, but combining psychotherapy and medication may only be useful in patients failing to respond to one treatment.     

Depression and treatment with antidepressants are associated with the development of gastro‐oesophageal reflux disease

Aliment Pharmacol Ther 31 , 1132–1140

Summary

Background The roles of depression and antidepressants in triggering reflux symptoms remain unclear. Aim To compare the incidence of gastro‐oesophageal reflux disease (GERD) in individuals with and without a depression diagnosis and to evaluate risk factors for a GERD diagnosis. The relationship between antidepressant treatment and GERD was also assessed. Methods The Health Improvement Network UK primary care database was used to identify patients with incident depression and an age‐ and sex‐matched control cohort with no depression diagnosis. Incident GERD diagnoses were identified during a mean follow‐up of 3.3 years. Furthermore, we performed nested case‐control analyses where odds ratios (OR) with 95% confidence intervals (CI) were estimated by unconditional logistic regression in multivariable models. Results The incidence of GERD was 14.2 per 1000 person‐years in the depression cohort and 8.3 per 1000 person‐years in the control cohort. The hazard ratio of GERD in patients with depression compared with controls was 1.72 (95% CI: 1.60–1.85). Among patients with depression, tricyclic antidepressant use was associated with an increased risk of GERD (OR: 1.71; 95% CI: 1.34–2.20), while selective serotonin reuptake inhibitors were not associated with GERD. Conclusions A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants.     

Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction

BackgroundContact hypersensitivity (CS) reaction in the skin is T-cell mediated immune reaction which plays a major role in the pathogenesis and chronicity of various inflammatory skin disorders and, like other delayed-type hypersensitivity (DTH) reactions, affords immunity against tumor cells and microbes. CS response is a self-limiting reaction, and interleukin (IL)-10 is considered to be a natural suppressant of cutaneous inflammatory response. Recently, it has been demonstrated that major depression is related to activation of the inflammatory response and elevation of some parameters of cell-mediated immunity. It has been suggested that such activation of the immune system may play a role in etiology of depression. If this immunoactivation is involved in etiology of depression, one would expect that antidepressant agents may have negative immunoregulatory effects. To the best of our knowledge, the effect of antidepressants on contact hypersensitivity has not been studied.MethodsThe aim of the present study was to establish the effect of prolonged desipramine or fluoxetine treatment on CS reaction to picryl chloride.ResultsAntidepressants significantly suppressed CS reaction, fluoxetine by 53% whereas desipramine by 47% compared to positive control. Moreover, desipramine and fluoxetine decreased relative weight of auxiliary lymph nodes. Desipramine decreased also relative weight of inguinal lymph nodes and spleens whereas desipramine and fluoxetine increased production of IL-10 in comparison to positive control.ConclusionThe observed effect of antidepressant drugs on CS reaction is consistent with the hypothesis that T-cell mediated immunity is targeted by antidepressants.     

Adaptive mechanisms following antidepressant drugs: Focus on serotonin 5-HT2A receptors

BackgroundThere is a strong support for the role of serotonin (5-HT) neurotransmission in depression and in the mechanism of action of antidepressants. Among 5-HT receptors, 5-HT_2A receptor subtype seems to be an important target implicated in the above disorder.MethodsThe aim of the study was to investigate the effects of antidepressants, such as imipramine (15 mg/kg), escitalopram (10 mg/kg) and tianeptine (10 mg/kg) as well as drugs with antidepressant activity, including N-acetylcysteine (100 mg/kg) and URB597 (a fatty acid amide hydrolase inhibitor, 0.3 mg/kg) on the 5-HT_2A receptor labeling pattern in selected rat brain regions. Following acute or chronic (14 days) drug administration, rat brains were analyzed by using autoradiography with the 5-HT_2A receptor antagonist [³H]ketanserin.ResultsSingle dose or chronic administration of imipramine decreased the radioligand binding in the claustrum and cortical subregions. The [³H]ketanserin binding either increased or decreased in cortical areas after acute N-acetylcysteine and URB597 administration, respectively. A similar shift towards reduction of the [³H]ketanserin binding was detected in the nucleus accumbens shell following either acute treatment with imipramine, escitalopram, N-acetylcysteine and URB597 or repeated administration of imipramine, tianeptine and URB597.ConclusionsIn conclusion, the present result indicate different sensitivity of brain 5-HT_2A receptors to antidepressant drugs depending on schedule of drug administration and rat brain regions. The decrease of accumbal shell 5-HT_2A receptor labeling by antidepressant drugs exhibiting different primary mechanism of action seems to be a common targeting mechanism associated with the outcome of depression treatment.     

A survey of prescribing preferences in the treatment of refractory depression: recent trends

The objective of this study was to gather data from a large group of clinicians on antidepressant prescribing practices in the treatment of refractory depression. Eight hundred and thirty-five clinicians about to attend the annual Massachusetts General Hospital psychopharmacology review course were asked to respond to a brief questionnaire regarding a hypothetical clinical case vignette. The case was of a patient who suffered from a new onset, unipolar, nonpsychotic, severe major depressive episode. Three hundred and four (36%) clinicians agreed to participate and filled out our questionnaire. Of the respondents, 260 (85.5%) indicated their preference for an initial treatment that combined medication and psychotherapy, as opposed to either modality alone. Furthermore, given this patient's nonresponse to two adequate selective serotonin reuptake inhibitor (SSRI) trials and one atypical antidepressant trial over an 8-month period, 39.8% of respondents indicated venlafaxine monotherapy as their next choice, whereas combining antidepressants (20.1%) and augmentation (18.4%) were the second and third most preferred treatment choices at this time point. Further on in the course of treatment, with the patient not having responded to any interventions during a 16-month period, 80.9% of survey respondents indicated electroconvulsant therapy (ECT) as their next preference. Among 304 clinicians surveyed, a combination of therapy and medication is the most preferred choice for treating severely depressed outpatients with new onset depression. Switching to venlafaxine, using two antidepressants together, and augmentation of an antidepressant regimen with a second agent accounted for 78.3% of respondents' preferences when faced with treating a depressed patient who had not responded to two adequate SSRI trials and one adequate atypical antidepressant trial. Of the respondents, 80.9% indicated ECT as a treatment preference after 16 months of multiple failed medication trials and nonresponse to psychotherapy. Further research is necessary to elucidate the factors that influence clinicians' reasoning for selecting one strategy over another.     

Poor response to antidepressants predicts new suicidal ideas and behavior in depressed outpatients

BackgroundOnly a few studies have investigated the factors associated with suicidal behavior after antidepressant treatment onset in adults. We examined the specific predictors of de novo suicidal ideas or attempts among depressed patients in the community, including subjects potentially at risk of suicidal behaviors, who initiated a new antidepressant treatment.MethodsA large set of GPs and psychiatrists throughout France followed-up, for 6 weeks, 4357 outpatients for whom an antidepressant drug was prescribed. Dimensions related with antidepressant-induced suicidal events, such as depression, anxiety or hopelessness, were assessed longitudinally using univariate and multivariate approaches among subjects with treatment-emergent suicide ideation or attempts.ResultsNew suicidal ideas were observed in 9% of patients with no suicidal ideation at baseline (n=81), while suicidal attempts were reported for 1.7% of the sample during the 6-week observation period (n=75). The onset of suicidal ideas and attempts was associated with the initial features of the patients (baseline level of anxiety, past history of suicide attempts and alcohol misuse) and the non-improvement of depression. Worsening of depressive symptoms during the follow-up increased the onset of new suicidal ideas (OR=5.67, p<0.001) and attempts (OR=2.60, p=0.002), corresponding to 67.5% and 56.5% of attributable risk respectively.ConclusionsWhen the analyses are restricted to the occurrence of suicidal ideas or attempts, the link between antidepressants and suicide risk might be more adequately explained by a poor response to antidepressant treatment rather than by a direct trigger-effect. This naturalistic study is limited by the use of non-structured diagnoses and self-report outcomes.     

Glutamate-Based Drug Discovery for Novel Antidepressants

ABSTRACT

Introduction: Classic antidepressants that modulate monoaminergic systems are not sufficiently effective and require long systematic application. Recent studies suggest that substances that modulate glutamatergic system may produce an antidepressant effect which is not only faster but also more sustained.

Areas covered: In this paper, the authors summarize the results of studies on antidepressant action of ketamine in patients with severe refractory depression, which have demonstrated high efficacy in a very short time after a single dose. Due to the adverse effects of ketamine that substantially exclude it from the daily use by patients, efforts have been made to find other NMDA receptor antagonists, which could mimic the therapeutic effect of ketamine but without the side effects. Intensive studies to elucidate ketamine’s mechanism of antidepressant action have also been conducted. Herein, the results of research showing that metabotropic glutamate (mGlu) receptors could be the target of novel antidepressants are also presented.

Expert opinion: The intensive preclinical and clinical research on NMDA and mGlu receptor ligands, which is currently going on, could contribute to the awaited breakthrough in the field of novel antidepressant drug discovery. This line of research may also lead to a new understanding of the biological basis of depression.     

Zinc deficiency alters responsiveness to antidepressant drugs in mice

BackgroundThere is some evidence coming from preclinical and clinical studies suggesting a relationship between dietary zinc intake and depressive symptoms. The aim of the study was to determine whether zinc deficiency alters the response to antidepressants with a different mechanism of action.We examine also whether these changes are related to activity of the hypothalamic-pituitary-adrenal HPA axis.MethodsMale CD-1 mice were assigned to groups according to diet and antidepressant administration. To evaluate animal behavior, the immobility time in the forced swim test (FST) and locomotor activity were measured. To determine serum zinc levels the flame atomic absorption spectroscopy (FAAS) was used. The serum corticosterone was determined by radioimmunoassay (RIA).ResultsAntidepressants administered to zinc-deprived mice induced an altered response in the FST when compared to animals fed with an adequate diet. There were no changes in locomotor activity. Animals subjected to a zinc-deficient diet showed a significant reduction in serum zinc levels, which was normalized by antidepressant treatment. An increase in serum corticosterone concentrations in mice fed with a zinc-deficient diet and treated with antidepressants was observed, so it can be concluded that reduced levels of zinc contribute hyperactivation of the HPA axis.ConclusionThe results of this study suggest that a diet with a reduced zinc level alters antidepressant action, which is associated with a reduction in the serum zinc level and rise in the corticosterone level. The results of this study may indicate the involvement of zinc deficiency in the pathogenesis of depression.     

The many faces of fatigue in major depressive disorder

Fatigue is a common complaint in the community and medical care settings. Different studies show a high comorbidity between fatigue and depressive disorder. Furthermore, fatigue is an important somatic symptom of depressive disorder and one of the main depressive presentations in primary-care medicine. Fatigue shows a slow response to antidepressant treatment and psychotherapy. Improved work performance is strongly correlated to improvement in energy. However, the assessment and treatment of fatigue in depressive disorder remains understudied. Different definitions of fatigue in depressive disorder are applied in DSM-IV and ICD-10, and depression rating scales all show a different coverage of this core depressive symptom, thereby hampering scientific research. Serotonin, norepinephrine, dopamine and histamine mediate symptoms of fatigue in depressive disorder. Although few data address the effect of antidepressants or augmentation strategies on fatigue-related symptoms, there is a pharmacological rationale for using antidepressant monotherapies, such as venlafaxine, bupropion, sertraline, fluoxetine, or augmentation of first-line treatment with stimulants or modafinil.