Concurrent Major Depression Research Articles

Epidemiology of suicidal feelings in an ageing Swedish population: from old to very old age in the Gothenburg H70 Birth Cohort Studies.

The first aim of this study was to provide prevalence suicidal feelings over time (past week, past month, past year and lifetime) in a population-based sample of old to very old adults without dementia. Does prevalence change with rising age? The second aim was to examine the fluctuation of suicidal feelings over time. How does this coincide with depression status? Data were derived from the Gothenburg H70 Birth Cohort Studies (the H70 studies) which are multidisciplinary longitudinal studies on ageing. A representative sample of adults in Gothenburg, Sweden with birth years 1901-1944 were invited to take part in a longitudinal health study on ageing and participated at one or more occasions during 1986-2014. The sample consisted of 6668 observations originating from 3972 participants without dementia between the ages of 70 and 108, including 1604 participants with multiple examination times. Suicidal feelings were examined during a psychiatric interview using the Paykel questions (life not worth living, death wishes, thoughts of taking own life, seriously considered taking life, attempted suicide). Prevalence figures for suicidal feelings of any severity were as follows: past week 4.8%, past month 6.7%, past year 11.2% and lifetime 25.2%. Prevalence rates increased with age in the total group and in women but not in men. Suicidal feelings were common in participants with concurrent major or minor depression, but over a third of the participants who reported suicidal feelings did not fulfil criteria for these diagnoses nor did they present elevated mean depressive symptom scores. The majority of participants consistently reported no experience of suicidal feelings over multiple examination times, but fluctuation was more common in women compared with men. Suicidal feelings in late-life are uncommon in individuals without depression indicating that such behaviour is not a widespread, normative phenomenon. However, such feelings may occur outside the context of depression.

Desvenlafaxine vs. placebo in the treatment of persistent depressive disorder

IntroductionPharmacotherapy of non-major persistent depressive disorder (PDD) is little studied. We report a study of the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine (DVLX) for PDD. MethodNon-psychotic, non-bipolar outpatients aged 20–65 having PDD without concurrent major depression (MDD) were randomized double-blind to desvenlafaxine or placebo for 12 weeks. All had Hamilton Depression Rating Scale (HDRS-24) score ≥ 12. Open-label DVLX was offered for 12 weeks following the acute trial. ResultsSeventy-one subjects having mean baseline HDRS-24 20.27 ± 4.77 were eligible, of whom post-RZ data was available for all 59 randomized. The primary 12 week analysis did not differentiate DVLX-treated subjects’ mean HDRS scores from those on placebo (6.53 ± 3.98 vs. 8.24 ± 4.96, F = 3.33, df = 1, p = .07). Several secondary analyses yielded statistically significant results, including Responder, CGI and QIDS. DiscussionAs the primary analysis did not reach statistical significance, this is a negative study which does not support the use of DVLX for non-major PDD. Nevertheless, statistically significant secondary analyses suggest the overall negative result could be due to sample size or sampling, suggesting further studies of this medication might be appropriate in this population.

Near-infrared spectroscopy (NIRS) and vagus somatosensory evoked potentials (VSEP) in the early diagnosis of Alzheimer's disease: rationale, design, methods, and first baseline data of the Vogel study.

Functional near-infrared spectroscopy (fNIRS) and vagus somatosensory evoked potentials (VSEP) show deviant patterns in subjects with Alzheimer's disease (AD) compared to healthy controls. We now aimed at testing the predictive value of these methods in the early diagnosis of AD. The Vogel study is a prospective, observational, long-term follow-up study with three time points of investigation within 6years. Residents of the city of Würzburg born between 1936 and 1941 were recruited. Every participant underwent physical, psychiatric, and laboratory examinations, and performed an intense neuropsychological testing as well as VSEP and NIRS according to the published procedures. 604 subjects were included. Mean age of the participants was 73.9±1.55years. The most frequent pathological physical and laboratory examination results were observed for blood pressure (62%), body weight (54%), HbA1c (16%), cholesterol (42%), and homocysteine (69%). Comprehensive analysis of cognitive testing showed mild cognitive impairment (MCI) in 12.3% of the patients. Concurrent major depression was found in 6.6% of the patients. We observed a high rate of MCI and somatic comorbidity in our cohort. The high rate of vascular risk factors and depressive symptoms, all of which are known risk factors of AD, is consistent with the notion that there are multiple options to prevent or postpone the onset of AD in a geriatric population like the one of the Vogel studies.

No Effect of Adding Brief Dynamic Therapy to Pharmacotherapy in the Treatment of Obsessive-Compulsive Disorder with Concurrent Major Depression

Background: Until now no studies have investigated the benefits of adding brief dynamic therapy (BDT) to medication in obsessive-compulsive disorder (OCD), while a number of recent investigations have demonstrated the efficacy of supplemental BDT among patients with major depressive disorders (MDD). The objective of the present study was to explore the efficacy of BDT combined with pharmacotherapy in comparison with pharmacotherapy alone in the treatment of OCD with concurrent MDD. Methods: A 12-month randomized clinical trial compared a standard selective serotonin reuptake inhibitor treatment with (n = 27) or without (n = 30) supplemental BDT in patients with OCD and concurrent MDD. Supplemental BDT was added during the first 16-week trial; all patients continued to be treated with only pharmacotherapy in the following continuation phase. The primary efficacy assessments were the Yale-Brown Obsessive Compulsive Scale and the 17-item Hamilton Rating Scale for Depression; the secondary efficacy measures included the Clinical Global Impression scale and the Global Assessment of Functioning. The data analysis was conducted on the ‘intent-to-treat (ITT) efficacy patient sample’. Results: Fifty patients completed the study. No difference between the 2 treatment groups was found at any point by any assessment method in the ITT study sample. Conclusions: Supplemental BDT in the treatment of patients with OCD with concurrent MDD who are receiving effective medication has no significant clinical effect on both obsessive and depressive symptoms.

Duloxetine in the treatment of irritable bowel syndrome: an open‐label pilot study

To assess the efficacy of duloxetine for irritable bowel syndrome (IBS). We conducted an open-label 12-week trial of duloxetine 60 mg daily in 15 patients with IBS without concurrent major depressive disorder. The primary outcome measure was average abdominal pain. Secondary measures included IBS symptoms, Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, IBS Quality-of-Life Scale, and Sheehan Disability Scale. We analyzed changes using random regression and one-sample t-tests. Fourteen patients completed at least one post-baseline evaluation; eight completed the study. Duloxetine was associated with significant improvement (p < 0.05) in pain, severity of illness, quality of life, loose stool, work and family disability, and anxiety. However, duloxetine did not improve hard stool. Although we found no evidence of serious duloxetine toxicity, seven participants withdrew over the course of the study because of adverse drug events. In this small, open-label study, duloxetine appeared to be effective for many features of IBS, but its adverse effects, most notably constipation, limited its use. Since our study excluded individuals with concurrent major depression, it appears that duloxetine may benefit IBS independently of its antidepressant effects. These encouraging but preliminary open-label findings support further investigation of duloxetine treatment in placebo-controlled trials of IBS.

Learning from the longitudinal course of concurrent traumatic life events, major depression and personality disorders

Learning from the longitudinal course of concurrent traumatic life events, major depression and personality disorders

Duloxetine Treatment of Dysthymia and Double Depression

Although not as common as major depressive disorder, dysthymia is not rare and is associated with substantial impairment. Antidepressants and some psychotherapies are often effective. We explored the efficacy of the antidepressant duloxetine, a serotonin and norepinephrine reuptake inhibitor. Between February 2005 and April 2006, we recruited 24 adults with DSM-IV dysthymia or dysthymia and concurrent major depression ("double depression") who had an entry score of > or = 17 on the clinician-rated Inventory for Depressive Symptomatology (IDS-C). We excluded subjects with significant medical illnesses and those requiring other psychotropic agents or undergoing psychotherapy. Subjects received duloxetine 60 mg/day for 6 weeks, increased as tolerated to 120 mg/day for the remainder of the 12-week trial for those with an inadequate treatment response. The subjects' mean +/- SD IDS-C scores decreased significantly from baseline (27.3 +/- 6.3) to endpoint (7.8 +/- 7.4, Student t = 12.38, df = 23, p < or = .001). The IDS-C response rate (intent-to-treat [ITT]) was 83% (20/24); the remission rate (ITT) was 79% (19/24). Among study completers, these rates were 89% (17/19) and 84% (16/19). Five subjects (21%) discontinued for side effects. Duloxetine appears to be an effective and well-tolerated treatment for dysthymia and double depression. A double-blind, placebo-controlled study is under way. If duloxetine is found to be effective, studies powered to detect potential, clinically important differences between duloxetine and other antidepressants will be needed. ClinicalTrials.gov identifier NCT00185575.

Quality of life in patients with Behçet's disease: the impact of major depression

Objective Behçet's disease (BD) is a multisystemic inflammatory disorder associated with high levels of depressive symptoms and lower quality of life (QoL). In this study, we aimed to investigate the impact of major depression (MD) on the QoL of patients with BD. Method BD outpatients ( n=25) and psychiatric outpatients ( n=25) with only MD among the Axis I psychiatric disorders, and BD outpatients ( n=25) and healthy controls ( n=25) without any Axis I psychiatric disorder were included in the study. The Structured Clinical Interview for DSM-IV (SCID-I) was used to determine Axis I psychiatric disorders. Depression and QoL levels were assessed with the Beck Depression Inventory (BDI) and the World Health Organization QoL Assessment–Brief (WHOQOL-BREF), respectively. Results There was no significant difference with regard to demographic characteristics between the groups. Psychiatric and BD patients with MD had significantly lower overall WHOQOL-BREF subscale scores than BD patients without MD and healthy controls. No significant difference was found in terms of QoL between the groups of psychiatric and BD patients with MD, nor between the groups of BD patients without MD and healthy controls. Overall, there was a significantly negative correlation between all WHOQOL-BREF subscale and BDI scores in BD patients. Conclusion The study suggests that concurrent MD has a negative impact on QoL of BD patients and that QoL is negatively correlated with the severity of depressive symptoms.

Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome

Fourteen patients (7 male, 7 female, 22-63 years), classified as having chronic fatigue syndrome (CFS), but without concurrent major depression, significant sleepiness or use of psychoactive medication, completed a double-blind, placebo-controlled, crossover study of the effects of the selective wakefulness-promoting agent, modafinil (200 and 400mg/day). The treatment periods were each 20 days, with washout periods of 2 weeks. The primary aim was to determine effects on cognition and the secondary aim was to determine effects on self-ratings of fatigue, quality of life and mood. Modafinil had mixed effects in two cognitive tasks. In a test of sustained attention, treatment with 200mg reduced the latency to correctly detect sequences, but 400mg increased the number of missed targets. In a test of spatial planning, the 200mg dose resulted in a slower initial thinking time for the easiest part of the task, whereas 400mg reduced the initial thinking time for the hardest part of the test. Lastly, in a test of mental flexibility and one of motor speed, patients performed worse whilst on modafinil (400mg), compared with the placebo period. No effects were observed on the performance of other psychometric tests or on self-ratings of fatigue, quality of life or mood, but this may have been due to insufficient statistical power. It is discussed whether the limited and mixed cognitive effects that we observed could have occurred by chance, or whether a subgroup of CFS patients with daytime sleepiness would have shown greater benefits.

Depression in Alzheimer’s disease: is there a temporal relationship between the onset of depression and the onset of dementia?

Alzheimer’s disease (AD) patients often present with concurrent major depression (MD). To investigate the reasons for this comorbidity, e.g. MD being a risk factor for AD, or both diagnoses having a common neurobiology, the temporal relationship between the first onset of AD and of MD during lifetime was investigated—57 out of 146 AD patients had a lifetime diagnosis of MD. The correlation between the ages at onset of MD and dementia was calculated. The incidence of MD in AD patients in several 5-year-intervals before and after the onset of AD was compared with the average incidence of MD in the present AD sample and with the expected incidence of MD in the general population. No significant correlation between the onset of AD and of MD could be found after controlling for age, gender and the Mini-Mental-State. However, the incidence of MD 5 years before and after the onset of AD significantly exceeded the expected incidences—MD is only partially related to AD. However, the increased incidence of MD within 5 years before and after the onset of dementia may indicate that a common neurobiological process causes cognitive decline and depression in a subsample of AD patients.

A comparison of paroxetine and amisulpride in the treatment of dysthymic disorder

Background: The purpose of this study was to provide preliminary data on the effects of paroxetine and amisulpride on depressive dimensions, analyzed by factor analysis, in dysthymic patients. Methods: One hundred and eighteen patients with DSM IV criteria for DD without concurrent major depression were enrolled in this 8-week, open study, and 100 completed it. Symptom dimensions were identified by principal components analysis with the SAS Factor procedure. Results: Results of the symptom rating scales indicated that both drugs were equally effective. Response rate was 65% both in the paroxetine and the amisulpride group and the proportions of patients achieving a final HRSD score ≤7 were 46.7 and 55%, respectively. MADRS factor analysis identified two factors at baseline: the first corresponding to the global severity of depression and the second to somatic symptoms. After 8 weeks of treatment only one factor could be substantiated. At week 4 both paroxetine and amisulpride produced significant improvements on factor 1 while at week 8 mean changes of factor 1 were greater in the amisulpride-treated patients. Limitations: The main limitation was the open-label design. Conclusions: Both paroxetine and amisulpride appear to be effective in the short-term management of DD, improving its most characteristic symptoms.

Major depression and insomnia in chronic pain.

Insomnia and depression are common problems for people with chronic pain, and previous research has found that each is correlated with measures of pain and disability. The goal of this study was to examine the combined impact of major depression and insomnia on individuals with chronic pain. The participants were patients with chronic musculoskeletal pain who underwent evaluation at an interdisciplinary treatment center. On the basis of semistructured interviews, participants were classified in three groups depending on whether they: (1) met criteria for major depression with insomnia (n = 38); (2) had insomnia without major depression (n = 58); or (3) had neither insomnia nor major depression (n = 47). The groups were then compared on self-report measures that included the McGill Pain Questionnaire, the Beck Depression Inventory, and the Multidimensional Pain Inventory. Participants with major depression and insomnia reported the most difficulty on measures of affective distress, life control, interference, and pain severity, although the insomniac patients without major depression also had elevated scores on some measures. In regression analyses, insomnia severity ratings did not contribute uniquely to the prediction of psychosocial problems when depression was controlled, but they did contribute to the prediction of pain severity. These results suggest that patients with chronic pain and concurrent major depression and insomnia report the highest levels of pain-related impairment, but insomnia in the absence of major depression is also associated with increased pain and distress.

Prevalence, incidence and stability of premenstrual dysphoric disorder in the community.

Despite an abundance of clinical research on premenstrual and menstrual symptoms, few epidemiological data provide estimates of the prevalence, incidence, co-morbidity, stability and correlates of premenstrual dysphoric disorder (PMDD) in the community. To describe the prevalence, incidence, 12 co-morbidity factors and correlates of threshold and subthreshold PMDD in a community sample of young women. Findings are based on prospective-longitudinal community survey of 1488 women aged 14-24, who were followed-up over a period of 48 months (follow-up, N = 1,251) as part of the EDSP sample. Diagnostic assessments were based on the Composite International Diagnostic Interview (CIDI) and its 12-month PMDD diagnostic module administered by clinical interviewers. Diagnoses were calculated using DSM-IV algorithms, but daily ratings of symptoms, as required, were not available. The baseline 12-month prevalence of DSM-IV PMDD was 5.8%. Application of the diagnostic exclusion rules with regard to concurrent major depression and dysthymia decreased the rate only slightly (5.3%). An additional 18.6 % were 'near-threshold' cases, mostly because they failed to meet the mandatory impairment criterion. Over the follow-up period only few new PMDD cases were observed: cumulative lifetime incidence was 7.4%. PMDD syndrome was stable across 48 months with < 10% complete remissions among baseline PMDD cases. The 12-month and lifetime co-morbidity rates were high (anxiety disorders 47.4%, mood disorders 22.9%; somatoform 28.4%), only 26.5 % had no other mental disorder. Particularly high odds ratios were found with nicotine dependence and PTSD. In terms of correlates increased rates of 4-weeks impairment days, high use of general health and mental health services, and increased rates of suicide attempts were found. In this sample of adolescents and young adults, premenstrual symptoms were widespread. However, DSM-IV PMDD was considerably less prevalent. PMDD is a relatively stable and impairing condition, with high rates of health service utilization, increased suicidality and substantial co-morbidity.

Maintenance desipramine for dysthymia: a placebo-controlled study

Background: This study examines the efficacy of maintenance pharmacotherapy in dysthymia without concurrent major depression, i.e. ‘pure dysthymia’. No published data exist on this topic. Methods: Responders to a 10-week open trial of desipramine (DMI) whose therapeutic response persisted during a 4-month continuation phase were eligible to begin a 2-year placebo-controlled maintenance phase. We analyzed the subgroup with DSM-III-R pure dysthymia ( n=27) that entered maintenance. Time to recurrence during maintenance therapy was compared between the two treatment groups. Results: Six of 13 patients receiving placebo and none of 14 patients receiving ongoing DMI experienced a recurrence. Risk of recurrence was significantly greater for placebo patients. Five of six placebo recurrences occurred within the first 6 months of maintenance. Limitations: Larger replication studies are needed. Conclusions: Desipramine was efficacious as a maintenance treatment in patients with pure dysthymia who responded to 7 months of acute and continuation DMI.

Treatment of Dysthymia With Sertraline

The selective serotonin reuptake inhibitor sertraline has been shown to be efficacious and well tolerated for the treatment of major depressive disorder. Relatively few trials, however, have examined the role of pharmacotherapy in dysthymia without concurrent major depression. The current investigation focuses on the use of sertraline for the treatment of dysthymia. In this 12-week, multicenter, double-blind study, 310 patients with a DSM-III-R diagnosis of dysthymic disorder without concurrent major depression were randomly assigned to receive either sertraline (N = 158) or placebo (N = 152). Sertraline was initiated at a dose of 50 mg daily, with titration permitted to a maximum of 200 mg daily. The primary evaluation criteria were the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Mean percentage reductions for the intent-to-treat population in SIGH-SAD scores were 44.6% for the sertraline-treated group and 33.2% for the placebo-treated group (p = .03); MADRS scores, 43.6% and 33.0% (p = .02); and CGI-S scores, 32.8% and 22.8% (p = .02). A significantly greater proportion of the sertraline-treated group was classified as responders (defined for HAM-D and MADRS scores as a 50% score reduction and for CGI-I as a score of 1 or 2 by the final visit) and remitters (SIGH-SAD score < or = 8) relative to the placebo-treated group by the final visit. In addition, sertraline-treated patients experienced greater improvements in all 9 domains of the Battelle Quality of Life Questionnaire than placebo-treated patients did, with a significant difference observed in favor of sertraline in 8 of the 9 domains. The life satisfaction and social interaction quality of life domains showed significantly greater response in sertraline responders compared with placebo SIGH-SAD responders. Sertraline was well tolerated. Thirteen percent of the sertraline-treated group versus 8% of the placebo-treated group withdrew from therapy owing to adverse events (p = .14). Sertraline is efficacious and well tolerated in the short-term treatment of dysthymia without concurrent major depression.

Neuropsychological Characteristics of the Dementia Syndrome of Depression: Onset, Resolution, and Three-Year Follow-Up

In this prospective double-blind study 13 hospitalized older adults with dementia syndrome of depression (DSD) were compared to 14 with Alzheimer's dementia with a concurrent major depression on a battery of neuropsychological tests. On admission to hospital (onset), patients with DSD differed from those with Alzheimer's dementia and depression only in that the former had stronger short-term verbal memory. Resolution of depression in patients with DSD resulted in a return to normal levels in most measures of verbal functioning, but nonverbal abilities remained impaired. Three years later those with DSD continued to cognitively outperform those with Alzheimer's dementia, indicating that treating depression in DSD appears to “buy back” up to 3 years of above-baseline cognitive functioning.

Higher serum prolyl endopeptidase activity in patients with post-traumatic stress disorder

Background: It is reported that psychiatric disorders, such as depression and schizophrenia, are associated with changes in serum activity of prolyl endopeptidase (EC 3.4.21.26), a cytosolic endopeptidase, which cleaves peptide bonds on the carboxylside of proline in proteins of relatively small molecular mass. Aims and methods: The aims of the present study were to examine serum PEP activity in patients with post-traumatic stress disorder (PTSD) versus healthy volunteers. PEP activity has been determined by a fluorimetric assay. Results: Serum PEP activity was significantly higher in patients with PTSD than in normal volunteers. Serum PEP activity was significantly higher in patients with PTSD and concurrent major depression than in patients with PTSD without major depression. In PTSD patients, there were no significant correlations between serum PEP activity and severity of PTSD symptoms. Conclusions: The results show that PTSD and, in particular, PTSD with concurrent major depression is associated with increased activity of PEP. Relevance: these results may be of importance for the (i) neuroendocrine pathophysiology of PTSD since PEP degrades neuropeptides, such as arginine vasopressin (AVP) and thyrotropin releasing hormone (TRH); and (ii) etiology of PTSD, since PEP degrades behaviorally active neuropeptides, such as AVP, TRH, oxytocin, neurotensin and substance P, which play a key role in positive reinforcement, social interactions, emotions and stress responsivity.

Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events

Background: Recently, it has been reported that serum interleukin-1β (IL-1β), but not soluble IL-2 receptor (sIL-2R), concentrations were significantly higher in patients with posttraumatic stress disorder (PTSD) than in normal volunteers, and that psychological stress in humans is associated with increased secretion of proinflammatory cytokines, such as IL-6. Methods: The aim of the present study was to examine the inflammatory response system in patients with PTSD through measurements of serum IL-6, sIL-6R, sgp130 (the IL-6 signal transducing protein), sIL-1R antagonist (sIL-1RA; an endogenous IL-1 receptor antagonist), CC16 (an endogenous anticytokine), and sCD8 (the T suppressor-cytotoxic antigen). Results: Serum IL-6 and sIL-6R, but not sgp130, sIL-RA, CC16, or sCD8, concentrations were significantly higher in PTSD patients than in normal volunteers. Serum sIL-6R concentrations were significantly higher in PTSD patients with concurrent major depression than in PTSD patients without major depression and normal volunteers. There were no significant relationships between serum IL-6 or sIL-6R and severity measures of PTSD. Conclusions: The results suggest that PTSD is associated with increased IL-6 signaling. It is hypothesized that stress-induced secretion of proinflammatory cytokines is involved in the catecholaminergic modulation of anxiety reactions.

Serotonergic and Noradrenergic Markers of Post-Traumatic Stress Disorder with and without Major Depression

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline (NE) may play roles in the pathophysiology of post-traumatic stress disorder (PTSD). This study examines (1) the availability of plasma total tryptophan, the precursor of 5-HT, and tyrosine, the precursor of NE; and (2) the platelet 5-HT transporter and α2-adrenoceptor (α2-AR) binding sites in patients with PTSD and healthy volunteers. High-performance liquid chromatography (HPLC) was employed to measure plasma tryptophan and tyrosine as well as amino acids known to compete with the same cerebral transport system; that is, valine, leucine, phenylalanine, and isoleucine. The maximum number of binding sites (Bmax) and their affinity (Kd) for binding to [3H]-paroxetine and [3H]-rauwolscine, a selective α2-AR antagonist, were determined. [3H]-paroxetine and [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD than in healthy volunteers. [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD and concurrent major depression (MD) than in PTSD patients without MD and healthy volunteers. Plasma tyrosine concentrations and the ratio of tyrosine/valine + leucine + isoleucine + phenylalanine + tryptophan were significantly higher in PTSD patients with MD than in those without MD and healthy volunteers. The results show that PTSD is accompanied by lower affinity of paroxetine binding sites and that PTSD with concurrent MD is accompanied by lower affinity of α2-ARs and increased plasma tyrosine availability to the brain. The results suggest that (1) serotonergic mechanisms, such as defects in the 5-HT transporter system, may play a role in the pathophysiology of PTSD; and (2) that catecholaminergic mechanisms, such as increased precursor availability and lowered affinity of α2-ARs, may play a role in the pathophysiology of PTSD with concurrent MD.

Pharmacotherapy of dysthymic and chronic depressive disorders: overview with focus on moclobemide

Chronic depression was once considered untreatable pharmacologically. Open studies conducted around 1980 demonstrated efficacious results with tricyclics, classical MAOIs and lithium in 45% of cases. The subsequent delineation of dysthymia in DSM-III and its future editions as well as ICD.10, facilitated controlled trials in subjects with “pure dysthymia” and those with superimposed major depression (so-called “double-depression”). TCAs, SSRIs, RIMA, and benzamides have all proven effective in an average of 65% vs. an average of 25% with placebo. Well tolerated compounds – e.g. moclobemide, sertraline and desipramine – may permit the long-term clinical management of this spectrum of dysthymic and related conditions. Patients with “lifetime pure dysthymia” tend to respond more slowly to antidepressants than those with concurrent major depression (“double-depression”) or those with “pure dysthymia” but with history of major depressive episodes. Chronicity is now well established; indeed discontinuation of antidepressants in a 4-year maintenance study has resulted in 89% rate of relapse. Dysthymia is a disabling condition and high doses of antidepressants are needed to achieve full recovery.