title: Long-term treatment of double depression: A preliminary study with serotonergic antidepressants A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia. Controlled efficacy study of fluoxetine in dysthymia. Effectiveness and cost-effectiveness of antidepressant treatment in primary health care: a six-month randomised study comparing fluoxetine to imipramine. Treatment of dysthymia and minor depression in primary care: A randomized controlled trial in older adults. Lost human capital from early-onset chronic depression. The treatment of chronic depression, part 1: study design and rationale for evaluating the comparative efficacy of sertraline and imipramine as acute, crossover, continuation, and maintenance phase therapies. A randomized double-blind study of fluoxetine versus placebo in the treatment of dysthymia. Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59 years. Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments. Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial in dysthymic patients without major depression. Escitalopram versus placebo in the treatment of dysthymic disorder The treatment of chronic depression, part 2: a double-blind, randomized trial of sertraline and imipramine. Imipramine and social-vocational adjustment in chronic depression. Treatment outcome validation of DSM-III depressive subtypes. Clinical usefulness in outpatients with mild to moderate depression. Interleukin-1 beta production in dysthymia before and after pharmacotherapy. Sertraline is more effective than imipramine in the treatment of non-melancholic depression:: Results from a multicentre, randomized study Ritanserin, imipramine, and placebo in the treatment of dysthymic disorder. Moclobemide and imipramine in chronic depression (dysthymia): an international double‐blind, placebo‐controlled trial Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder. THE NOTTINGHAM STUDY OF NEUROTIC DISORDER: COMPARISON OF DRUG AND PSYCHOLOGICAL TREATMENTS
abstract: 1 . There is increasing evidence that many patients with major depression also have coexisting dysthymia , and that antidepressant treatment may alleviate both conditions . 2 . Open-label study of fluoxetine and trazodone for 18 patients meeting DSM-III-R criteria for concurrent dysthymia and major depression . 3 . Fourteen patients completed three-month medication trials , and seven ( 50 % ) of completers ) responded to treatment . At five months , eight ( 57.1 % ) were in remission .  Fluoxetine was significantly better tolerated than trazodone , with respective dropout rates of 7.7 % and 80 % . 4 . Findings are consistent with efficacy of serotonergic agents in this condition BACKGROUND Despite the high prevalence of dysthymia and its associated morbidity , few controlled trials have evaluated the efficacy of antidepressant medication for this disorder . A 12-week , double-blind , placebo-controlled , r and omized , multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia . METHODS A total of 416 out patients ( 271 women and 145 men ) aged 25 to 65 years with DSM-III-R-defined , early-onset , primary dysthymia without concurrent major depression were r and omized to 12 weeks of treatment with  sertraline , imipramine , or placebo . RESULTS Both active treatments result ed in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression ( P = .04 and P = .01 for sertraline and imipramine vs placebo , respectively ) , the Montgomery-Asberg Depression Rating Scale ( P = .01 and P = .003 vs placebo , respectively ) , Hopkins Symptom Checklist ( P < .05 ) , and the self-rated version of the Inventory of Depressive Symptoms ( P < .05 ) . With the use of a Clinical Global impressions improvement score of 1 or 2 ( very much or much improved ) to define response , response rates were 59 % for sertraline , 64 % for imipramine , and 44 % for placebo ( P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo ) . A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events ( P = .001 and P < .001 , respectively ) . CONCLUSIONS Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder , with both sertraline and imipramine being more effective than placebo . The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia , which may require prolonged treatment with antidepressant medication BACKGROUND There have been very few controlled studies of antidepressants in dysthymia , particularly in sample s diagnosed reliably and with an adequate length of follow-up . In this investigation , we measured the long-term outcome in a large group of patients meeting DSM-III-R criteria for dysthymia . This study was design ed to investigate whether fluoxetine is effective in the treatment of dysthymia . METHOD This r and omised study including 140 patients , compared  fluoxetine ( 91 patients ) and placebo ( 49 patients ) on a double-blind basis in two distinct phases : a short-term end-point ( 3 months with 20 mg/day fluoxetine ) and a medium-term end-point ( 6 months ) where the initial responders continued double-blind treatment unchanged and non-responders received an additional treatment of 20 mg/day fluoxetine . RESULTS After three months of treatment , response was seen more frequently in the fluoxetine group ( 42/72 ) than in the placebo group ( 14/39 , P < 0.0001 ) . Improved patients at 3 months were still improved at 6 months . Furthermore , 50 % of the nonresponders at 3 months improved and rated as responders at 6 months , after fluoxetine was increased to 40 mg daily . CONCLUSIONS This study showed the significant and persistent action of fluoxetine on dysthymia . The finding that 50 % of the non-responders at 3 months were improved at 6 months , after fluoxetine dosage was increased to 40 mg daily , argues in favour of treating dysthymic patients for at least 6 months , and with a higher dosage if the initial doses are ineffective BACKGROUND Over the past decade , studies of the effectiveness of pharmacological treatment for depression have often been based on research design s intended to measure efficacy , and for this reason the results are of limited generalizability . Research is needed comparing the clinical and economic outcomes of antidepressants in day-to-day clinical practice . METHODS A six-month r and omised prospect i ve naturalistic study comparing fluoxetine to imipramine carried out in three primary care health centres . Outcome measures were the Montgomery Asberg Depression Rating Scale ( MADRS ) , direct costs , indirect costs and total costs . Subjects were evaluated at the beginning of treatment and at one , three and six months thereafter . RESULTS Of the 103 patients , 38.8 % ( n = 40 ) were diagnosed with major depressive disorder , 14.6 % ( n = 15 ) with dysthymic disorder , and 46.6 % ( n = 48 ) with depressive disorder not otherwise specified . Patients with major depressive disorder or dysthymic disorder achieved similar clinical improvement in both treatment groups ( mean MADRS ratings decrease in major depressive disorder from baseline to 6 months of 18.3 for imipramine and 18.8 for fluoxetine ) . For patients with major depressive disorder and dysthymic disorder , the imipramine group had fewer treatment-associated costs ( imipramine 469.66 Euro versus fluoxetine 1,585.93 Euro in major depressive disorder , p < 0.05 ; imipramine 175.39 Euro versus fluoxetine 2,929.36 Euro in dysthymic disorder , p < 0.05 ) . The group with depressive disorder not otherwise specified did not experience statistically significant differences in clinical and costs outcomes between treatment groups . LIMITATIONS Exclusion criteria , participating physicians may not represent GPs . CONCLUSIONS In a primary care context , imipramine may represent a more cost-effective treatment option than fluoxetine for treating major depressive disorder or dysthymic disorder . There were no differences in cost-effectiveness in the treatment of depressive disorder not otherwise specified CONTEXT Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia . OBJECTIVE To compare the effectiveness of pharmacotherapy and psychotherapy in primary care setting s among older persons with minor depression or dysthymia . DESIGN R and omized , placebo-controlled trial ( November 1995-August 1998 ) . SETTING Four geographically and clinical ly diverse primary care practice s. PARTICIPANTS A total of 415 primary care patients ( mean age , 71 years ) with minor depression ( n = 204 ) or dysthymia ( n = 211 ) and a Hamilton Depression Rating Scale ( HDRS ) score of at least 10 were r and omized ; 311 ( 74.9 % ) completed all study visits . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 137 ) or placebo ( n = 140 ) , starting at 10 mg/d and titrated to a maximum of 40 mg/d , or problem-solving treatment- primary care ( PST-PC ; n = 138 ) . For the paroxetine and placebo groups , the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring ; for the PST-PC group , visits were for psychotherapy . MAIN OUTCOME MEASURES Depressive symptoms , by the 20-item Hopkins Symptom Checklist Depression Scale ( HSCL-D-20 ) and the HDRS ; and functional status , by the Medical Outcomes Study Short-Form 36 ( SF-36 ) physical and mental components . RESULTS Paroxetine patients showed greater ( difference in mean [ SE ] 11-week change in HSCL-D-20 scores , 0.21 [ 0 . 07 ] ; P = .004 ) symptom resolution than placebo patients . Patients treated with PST-PC did not show more improvement than placebo ( difference in mean [ SE ] change in HSCL-D-20 scores , 0.11 [ 0.13 ] ; P = .13 ) , but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks ( P = .01 ) . For dysthymia , paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high ( difference in mean [ SE ] change in SF-36 mental component scores , 5.8 [ 2.02 ] ; P = . 01 ) or intermediate ( difference in mean [ SE ] change in SF-36 mental component scores , 4.4 [ 1.74 ] ; P = .03 ) . Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo ( P>/=.12 for low- , intermediate- , and high-functioning groups ) . For minor depression , both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning ( difference vs placebo in mean [ SE ] change in SF-36 mental component scores , 4.7 [ 2.03 ] for those taking paroxetine ; 4.7 [ 1.96 ] for the PST-PC treatment ; P = .02 vs placebo ) . CONCLUSIONS Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression . The benefits of PST-PC were smaller , had slower onset , and were more subject to site differences than those of paroxetine OBJECTIVE Chronic depression starts at an early age for many individuals and could affect their accumulation of " human capital " ( i.e. , education , higher amounts of which can broaden occupational choice and increase earnings potential ) . The authors examined the impact , by gender , of early- ( before age 22 ) versus late-onset major depressive disorder on educational attainment . They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset , as well as never-occurring , major depressive disorder on expected lifetime earnings . METHOD The authors used logistic and multivariate regression methods to analyze data from a three-phase , multicenter , double-blind , r and omized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older . These data were integrated with U.S. Census Bureau data on 1995 earnings by age , educational attainment , and gender . RESULTS Early-onset major depressive disorder adversely affected the educational attainment of women but not of men . No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or , for subjects rated as having responded , after 76 weeks of maintenance treatment . A r and omly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18 % lower than those of a r and omly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all . CONCLUSIONS Early-onset major depressive disorder causes substantial human capital loss , particularly for women . Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits BACKGROUND Chronic depressions are common , disabling , and undertreated , and prior chronicity predicts future chronicity . However , few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning . METHOD We describe the design and rationale for 2 parallel double-blind , r and omized , multicenter acute and maintenance phase treatment trials . One focused on DSM-III-R major depression currently in a chronic ( > or = 2 years ) major depressive episode , the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ( " double depression " ) . RESULTS Considering the critical knowledge deficits , we design ed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine , followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response . Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo ; those taking imipramine continued without a placebo substitution . As part of the acute trial , subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over ( double-blind ) to the alternative medication for a 12-week acute phase trial . We obtained naturalistic follow-up data ( up to 18 months ) for subjects exiting the protocol at any time . CONCLUSION Multiphase protocol s for chronic depression can test efficacy by r and omized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program OBJECTIVE The purpose of this study was to assess the efficacy of fluoxetine , a selective serotonergic antidepressant , in the treatment of  dysthymia .  METHOD Thirty-five patients who met criteria for dysthymia , but not major depression , began r and omized , double-blind 8-week trials of fluoxetine or placebo . RESULTS Of 32 patients who completed the study , 10 ( 62.5 % ) of the 16 patients given fluoxetine and three ( 18.8 % ) of the 16 given placebo responded to treatment . Response was defined as 1 ) 50 % or greater decrease in Hamilton Rating Scale for Depression score and 2 ) a score of 1 or 2 on the Clinical Global Impression ( CGI ) improvement subscale .  Fluoxetine subjects showed significantly greater improvement at week 8 than placebo subjects on the Hamilton depression and CGI scales , but not on the Hopkins Symptom Check-list ( 58-item ) or the Cornell Dysthymia Rating Scale . CONCLUSIONS When compared to placebo , fluoxetine showed short-term effectiveness in treating dysthymic symptoms OBJECTIVE The research ers evaluated the effectiveness of paroxetine and Problem-Solving Treatment for Primary Care ( PST-PC ) for patients with minor depression or dysthymia . STUDY DESIGN This was an 11-week r and omized placebo-controlled trial conducted in primary care practice s in 2 communities ( Lebanon , NH , and Seattle , Wash ) .  Paroxetine ( n=80 ) or placebo ( n=81 ) therapy was started at 10 mg per day and increased to a maximum 40 mg per day , or PST-PC was provided ( n=80 ) . There were 6 scheduled visits for all treatment conditions . POPULATION A total of 241 primary care patients with minor depression ( n=114 ) or dysthymia ( n=127 ) were included . Of these , 191 patients ( 79.3 % ) completed all treatment visits . OUTCOMES Depressive symptoms were measured using the 20-item Hopkins Depression Scale ( HSCL-D-20 ) . Remission was scored on the Hamilton Depression Rating Scale ( HDRS ) as less than or equal to 6 at 11 weeks . Functional status was measured with the physical health component ( PHC ) and mental health component ( MHC ) of the 36-item Medical Outcomes Study Short Form . RESULTS All treatment conditions showed a significant decline in depressive symptoms over the 11-week period . There were no significant differences between the interventions or by diagnosis . For dysthymia the remission rate for paroxetine ( 80 % ) and PST-PC ( 57 % ) was significantly higher than for placebo ( 44 % , P=.008 ) . The remission rate was high for minor depression ( 64 % ) and similar for each treatment group . For the MHC there were significant outcome differences related to baseline level for paroxetine compared with placebo . For the PHC there were no significant differences between the treatment groups . CONCLUSIONS For dysthymia , paroxetine and PST-PC improved remission compared with placebo plus nonspecific clinical management . Results varied for the other outcomes measured . For minor depression , the 3 interventions were equally effective ; general clinical management ( watchful waiting ) is an appropriate treatment option OBJECTIVE This study assessed the efficacy of antidepressant treatment ( sertraline ) and group cognitive behavior therapy , alone or in combination , in primary dysthymia . The clinical features of dysthymia , as well as the functional impairments associated with the illness ( e.g. , quality of life , stress perception , coping styles ) , were evaluated . METHOD Patients ( N = 97 ) diagnosed with primary dysthymia , but no other current comorbid disorder , received either sertraline or placebo in a double-blind design over 12 weeks . In addition , a subgroup of the patients ( N = 49 ) received a structured , weekly group cognitive behavior therapy intervention . RESULTS Treatment with sertraline , with or without group cognitive behavior therapy , reduced the functional impairment of depression . The reductions were similar in the drug-cognitive therapy group and in subjects who received the drug alone . Furthermore , while group cognitive behavior therapy alone reduced the depression scores , this effect was not significantly greater than the effect of the placebo . The drug treatment also induced pronounced improvement in the functional measures , and in some respects these effects were augmented by group cognitive behavior therapy . Among patients who responded favorably to cognitive behavior therapy , the improvements in the functional measures were similar to those who responded to drug treatment , whereas such functional changes were not seen among patients who responded to placebo . CONCLUSIONS Sertraline treatment effectively reduces the clinical symptoms and functional impairments associated with dysthymia . Although the group cognitive behavior therapy intervention was less effective in alleviating clinical symptoms , it augmented the effects of sertraline with respect to some functional changes , and in a subgroup of patients it attenuated the functional impairments characteristic of dysthymia BACKGROUND 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 . METHOD In this 12-week , multicenter , double-blind study , 310 patients with a DSM-III-R diagnosis of dysthymic disorder without concurrent major depression were r and omly 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 . RESULTS 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 Question naire 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 ) . CONCLUSION Sertraline is efficacious and well tolerated in the short-term treatment of dysthymia without concurrent major depression Numerous studies have assessed the acute efficacy of antidepressants , including selective serotonin reuptake inhibitors , in treating dysthymic disorder ; however , escitalopram , the S-enantiomer of citalopram , has not been studied . Thirty-six out patients with Structured Clinical Interview for DSM-III-R-diagnosed dysthymic disorder , aged 23–65 years ( mean±SD=44.7±11 years ) , were r and omly assigned to double-blind escitalopram ( maximum dose 20 mg/day ) versus placebo for 12 weeks . Inclusion criteria included age 18–65 years and Hamilton Depression Rating Scale ( HDRS ) score ≥12 . We hypothesized that escitalopram would be superior to placebo in the HDRS-24 item total score at week 12 . We also hypothesized the superiority of escitalopram over placebo for secondary measures , including the percentage of participants classified as responders and remitters , as well as social functioning ( Social Adjustment Scale ) , clinical global impression-improvement , Global Assessment of Functioning Scale . Participants ' baseline HDRS-24 averaged 23.4±5.9 . Final HDRS-24 scores at last observation carried forward did not differ significantly between escitalopram-treated  ( mean±SD=10.88±5.83 ) and placebo-treated  individuals ( mean±SD=16.4±6.34 ) ( F=2.82 , degrees of freedom=1,32 , P=0.10 ) . Significant differences favoring active medication were found on the Social Adjustment Scale and the Clinical Global Impression Severity and Global Assessment of Functioning Scale , but not in the percentages of responders or remitters . A larger study sample or higher escitalopram dose may show more significant placebo – medication differences BACKGROUND Chronic depression appears to be a common , frequently disabling illness that is often inadequately treated . Unlike episodic depressions with shorter illness duration , neither acute nor long-term treatment approaches for chronic depression have been well studied . METHOD 635 out patients at 12 sites who met DSM-III-R criteria for chronic major depression or double depression were r and omly assigned to 12 weeks of double-blind treatment with either sertraline ( in daily doses of 50 - 200 mg ) or imipramine ( in daily doses of 50 - 300 mg ) . Efficacy and safety were assessed either weekly or every 2 weeks during the 12 weeks of acute treatment . RESULTS Despite high rates of chronicity ( mean duration of major depression = 8.9+/-9.1 years ; mean duration of dysthymia = 23+/-13 years ) and high rates of comorbidity , 52 % of patients achieved a satisfactory therapeutic response to sertraline or imipramine ( by a conservative , intent-to-treat analysis ) . Approximately 21 % of the patients who had achieved a therapeutic response at week 12 had not done so at week 8 , confirming the longer time to response in depressions with high chronicity . Patients treated with sertraline reported significantly fewer adverse events and were significantly less likely to discontinue treatment due to side effects than imipramine-treated patients ( 6.3 % vs. 12.0 % ) . CONCLUSION These results indicate that patients suffering from depression with high chronicity can achieve a good therapeutic response to acute treatment with either sertraline or imipramine , although sertraline is better tolerated The authors compared the effects of 6 weeks of imipramine treatment with 6 weeks of placebo treatment on  social and vocational impairment in chronic depression .  Imipramine was associated with significantly greater pre- to posttreatment improvement of social-vocational impairments in chronic depression , suggesting that these impairments may have represented affective symptoms rather than characterologic deficits An algorithm for transcribing Research Diagnostic Criteria diagnoses for depressive disorders to similar categories in the DSM-III was applied to 103 depressed out patients previously diagnosed by Research Diagnostic Criteria . All had Hamilton Depression Rating Scale scores of 18 or less . Among 64 patients completing a six-week , double-blind study comparing desipramine hydrochloride with placebo , desipramine was significantly more effective than placebo in patients with DSM-III major depression but not in those with dysthymic disorder . Among patients with major depression , a significant drug-placebo response difference was demonstrated even in those without melancholia . These findings support the clinical usefulness of the DSM-III in the treatment of depressed out patients . Independent of DSM-III diagnosis , however , evidence of panic attacks seemed to identify patients who benefited from desipramine therapy . This suggests that the DSM-III hierarchy , which excludes consideration of panic in patients with major depression , may require revision BACKGROUND Like major depression , dysthymia has been associated with elevated production of interleukin-1 ( IL-1 beta ) in mitogen-stimulated lymphocytes . In the present investigation , we assessed whether the elevated IL-1 beta production in dysthymic patients would normalize following treatment with sertraline . METHODS The production of IL-1 beta was determined in dysthymic patients and in nondepressed control subjects . Patients then received 12 weeks of doses of either sertraline or placebo in a double-blind trial , after which cytokine production was again determined . RESULTS Basal IL-1 beta was elevated in dysthymic patients relative to control subjects . Cytokine production was modestly correlated with the severity of symptoms and with the age of illness onset . Relative to placebo treatment , sertraline attenuated the symptoms of depression ; however , this was not accompanied by normalization of IL-1 beta production . CONCLUSIONS While dysthymia is associated with elevated IL-1 beta production , the failure for the cytokine to normalize following symptom alleviation suggests that either the IL-1 beta may be a trait marker of the illness , or that more sustained treatment is necessary to reduce cytokine production . Given the neuroendocrine and central neurochemical consequences of exogenously administered IL-1 beta , the possibility ought to be explored that increased IL-1 beta production may play a role in the pathophysiology of dysthymia The acute treatment efficacy , tolerability , and effects on health-related quality of life of sertraline ( 50 - 200 mg/day ) versus imipramine ( 75 - 225 mg/day ) were compared in out patients with non-melancholic depression . The study employed an open-label , parallel-group design . One hundred and sixteen patients were r and omized to receive sertraline and 123 to receive imipramine for 8 weeks . In the intent-to-treat ( ITT ) , last-observation-carried-forward ( LOCF ) analysis , sertraline produced statistically significantly greater improvements in depressive ( 21-item Hamilton Depression Rating Scale [ HAM-D(21 ) ] scores of 24.9 and 24.4 were reduced to 10.3 and 13.1 at endpoint , P<.005 ) and anxiety symptoms ( Hamilton Anxiety Rating Scale [ HAM-A ] scores of 21.8 and 21.9 were reduced to 9.5 and 13.9 , P<.01 ) , as well as in response ( 69.0 % versus 53.7 % at endpoint , P=.016 ) and remission rates ( 51.3 % versus 38.0 % at endpoint , P=.041 ) from week 4 onwards compared with imipramine . The proportion of patients who were ' very much improved ' or ' much improved ' ( Clinical Global Impressions Scale of Improvement [ CGI-I ] score of 1 or 2 ) was significantly higher at endpoint in the sertraline group ( 76.1 % ) than in the imipramine group ( 62.8 % ) ( P=.028 ) . At week 8 , patients in both treatment groups showed clear improvements in quality of life , although nonstatistically significant differences were evident in the quality of life of sertraline- versus imipramine-treated patients . Sertraline was significantly superior in tolerability with less discontinuations due to adverse events ( 10.3 % ) compared with the imipramine group ( 24.4 % ) ( P=.004 ) . It was concluded that sertraline is more effective than imipramine in the acute treatment of depressive and anxiety symptoms in patients with non-melancholic depression Fifty out patients with dysthymic disorder ( DSM-III ) were divided by double-blind r and omized assignment into three groups given ritanserin , imipramine , and placebo , respectively . The trial was of 7 weeks ' duration ; by week 6 , imipramine was clearly superior to placebo , whereas by week 7 , both drugs caused significantly more improvement than the placebo . Although imipramine had slightly greater efficacy than ritanserin , it also had significantly more side effects . This was particularly evident in the higher dropout rate with imipramine . The efficacy and side effect profile of ritanserin makes it well tolerated and acceptable with  dysthymic patients who , although they do not respond as quickly as patients with major depressive disorder , do show significant improvement , given sufficient time An international , multicenter , placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide , a new reversible inhibitor of monoamine oxidase A , and imipramine in the treatment of dysthymia ( DSM-III R ) . A total of 315 patients were enrolled and r and omly assigned to an 8-week treatment in one of three groups ( moclobemide . imipramine and placebo ) . Patients were male or female out patients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia , primary type , with late or early onset . Of the patients in each group 85 % completed the 8-week treatment period . The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment end-point was significantly higher in the moclobemide ( 60 % ) and imipramine ( 49 % ) treatment groups than in the placebo group ( 22 % ) . Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables ( i.e. Hamilton Rating Scale for Depression , final overall efficacy assessment , Clinical ( Global Impression and symptom check list self rating ) , A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression , as well as in early and late onset subgroups . In early onset cases , moclobemide was significantly more effective than was imipramine on the Ramilton Rating Scale for Depression . Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo , and the investigators ' final overall assessment of tolerability significantly favoured mociohemide over imipramine . This study demonstrates the efficacy of high dose moclobemide ( mean dose 675mg/day ) and high dose imipramine ( 220 mg/day ) against placebo in the treatment of dysthymia .  Moclobemide was better tolerated than was imipramine OBJECTIVE The authors compared the efficacy and side effects of fluoxetine and placebo in elderly out patients with dysthymic disorder . METHODS Patients were r and omly assigned to fluoxetine ( 20 mg-60 mg/day ) or placebo for 12 weeks in a double-blind trial . RESULTS Of 90 r and omized patients , 71 completed the trial . In the intent-to-treat sample , r and om regression analyses of the Hamilton Rating Scale for Depression ( Ham-D ; 24-item ) and Cornell Dysthymia Rating Scale ( CDRS ) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group . Analysis of percentage change in Ham-D scores yielded no effect for treatment group , but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group , favoring fluoxetine over placebo . In the intent-to-treat sample , response rates were 27.3 % for fluoxetine and 19.6 % for placebo . In the completer sample , response rates were 37.5 % for fluoxetine and 23.1 % for placebo . CONCLUSION Fluoxetine had limited efficacy in elderly dysthymic patients . The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults , and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients . Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder , and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance 210 psychiatric out patients with generalised anxiety disorder ( 71 ) , or panic disorder ( 74 ) , or dysthymic disorder ( 65 ) diagnosed by an interview schedule for DSM-III were allocated by constrained r and omisation to one of five treatments : diazepam ( 28 ) , dothiepin ( 28 ) , placebo ( 28 ) , cognitive and behaviour therapy ( 84 ) , and a self-help treatment programme ( 42 ) . All treatments were given for 6 weeks and then withdrawn by 10 weeks . Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2 , 4 , 6 , and 10 weeks after r and omisation . 18 patients had insufficient data for analysis because of early drop-out . There were no important differences in treatment response between the diagnostic groups , but diazepam was less effective than dothiepin , cognitive and behaviour therapy , or self-help , these three treatments being of similar efficacy . Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period , and those allocated to dothiepin and cognitive and behaviour therapy took the least
target: CONCLUSIONS This systematic review provides evidence for the efficacy of both SSRIs and TCAs in the treatment of chronic depression and showed a better acceptability of SSRIs
background: INTRODUCTION Chronic depression represents a substantial portion of depressive disorders and is associated with severe consequences .
  This review examined the efficacy and acceptability of selective serotonin reuptake inhibitors ( SSRIs ) and tricyclic antidepressants ( TCAs ) in the treatment of chronic depression .
  Additionally , the comparative effectiveness of the two types of antidepressants has been examined .