Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial. Combination of inositol and serotonin reuptake inhibitors in the treatment of depression Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients. Reboxetine, the first selective noradrenaline reuptake inhibitor antidepressant: Efficacy and tolerability in 2613 patients Antidepressants and driving ability: results from a clinical study. Treatment of Post-Myocardial Infarction Depressive Disorder: A Randomized, Placebo-Controlled Trial With Mirtazapine Gender differences in treatment response to sertraline versus imipramine in chronic depression. A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. Fluoxetine versus trimipramine in the treatment of depression in geriatric patients. Treatment of depression in patients with breast cancer: a comparison between paroxetine and amitriptyline Efficacy and Tolerability of Reboxetine Compared with Citalopram: A Double-blind Study in Patients with Major Depressive Disorder Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. Fluoxetine, but not Tricyclic Antidepressants, Potentiates the 5-Hydroxytryptophan-Mediated Increase in Plasma Cortisol and Prolactin Secretion in Subjects with Major Depression or with Obsessive Compulsive Disorder Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Citalopram versus desipramine in treatment resistant depression: Effect of continuation or switching strategies. A randomized open study A controlled trial of antidepressants in patients with Parkinson disease and depression A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache. Differential actions of antidepressant treatments on cardiac autonomic alterations in depression: A prospective comparison. Monoamine oxidase inhibitors revisited: what you should know. Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model. Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women's Health Initiative study. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice.
BACKGROUND The cost-effectiveness of tricyclic antidepressants ( TCAs ) and selective serotonin reuptake inhibitors ( SSRIs ) has not been compared in a prospect i ve study in primary care . AIMS To determine the relative cost-effectiveness of TCAs , SSRIs and lofepramine in UK primary care . METHOD An open-label , three-arm r and omised trial with a preference arm . Practitioners referred 327 patients with incident depression . RESULTS No significant differences were found in effectiveness or cost-effectiveness . The numbers of depression-free weeks over 12 months ( on the Hospital Anxiety and Depression Scale ) were 25.3 ( 95 % CI 21.3 - 29.0 ) for TCAs , 28.3 ( 95 % CI 24.3 - 32.2 ) for SSRIs and 24.6 ( 95 % CI 20.6 - 28.9 ) for lofepramine .  Mean health service costs per patient were pound 762 ( 95 % CI 553 - 1059 ) for TCAs , pound 875 ( 95 % CI 675 - 1355 ) for SSRIs and pound 867 ( 95 % CI 634 - 1521 ) for lofepramine .  Cost-effectiveness acceptability curves suggested SSRIs were most cost-effective ( with a probability of up to 0.6 ) . CONCLUSIONS The findings support a policy of recommending SSRIs as first-choice antidepressants in primary care BACKGROUND Inositol has been reported to be an effective treatment in depression , and we hypothesized that inositol addition might enhance or speed up response to  serotonin selective reuptake inhibitors ( SSRI ) . METHODS Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol .  Hamilton Depression Rating Scale was used as an assessment tool at baseline , and 1 , 2 , 3 , and 4 weeks . RESULTS No significant difference was found between the two treatment groups . CONCLUSIONS Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [ e.g. , monoamine oxidase inhibitors ( MAOI ) plus tricyclic antidepressants ( TCA ) , TCA plus lithium ] . By contrast , augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol BACKGROUND Whether the Brain Derived Neurotrophic Factor ( BDNF ) Val66Met polymorphism can predict antidepressant drug efficacy in depressed patients remains unclear , suggesting that it may depend on antidepressant classes . We assessed the impact of Val66Met polymorphism on antidepressant response and remission depending on antidepressant classes . METHODS In a 6-month prospect i ve , real-world setting , treatment study , 345 Caucasian depressed patients requiring a new or different drug treatment with a selective serotonin reuptake inhibitor ( SSRI ) , a serotonin and noradrenalin reuptake inhibitor ( SNRI ) or a tricyclic antidepressant ( TCA )  , were genotyped and assessed for response and remission . RESULTS 231 ( 67 % ) patients were homozygous for the Val66 allele ( Val/Val ) and 114 ( 33 % ) were carriers of Met allele ( Met ) . 152 ( 44.1 % ) patients were treated with SSRI , the others with SNRI/TCA . Both response and remission were explained by interactions between the Val66Met polymorphism and antidepressant drug classes ( multivariate models adjusted for propensity-scores : p=0.02 and p=0.03 respectively ) . With SSRI , Val/Val patients had a higher response rate 3 months post-treatment than Met patients ( 68.1 % versus 44 % ; adjusted-OR : 3.04 , IC95 % [ 1.05 ; 9.37 ] , p=0.04 ) . With SNRI/TCA , Val/Val patients had a lower remission rate 6 months post-treatment than Met patients ( 33.3 % versus 60.9 % , adjusted-OR : 0.27 , IC95 % [ 0.09 ; 0.76 ] , p=0.02 ) . LIMITATIONS Limited sample size . CONCLUSIONS This study argues for a personalized prescription of antidepressants in Caucasian patients with major depressive disorder , based on the BDNF Val66Met polymorphism : SSRI should be preferred for Val/Val patients and SNRI/TCA for Met patients . Further studies are required to confirm these data INTRODUCTION : Reboxetine is the first available selective noradrenaline re-uptake inhibitor ( selective NRI ) . This paper gives an overview of its antidepressant efficacy and tolerability in eight r and omized double-blind , multicentre clinical trials . The clinical profile of reboxetine is also compared with that of the tricyclic antidepressants ( TCAs ) desipramine and imipramine and the selective serotonin re-uptake inhibitor ( SSRI ) fluoxetine . METHODS : Pooled data were analysed from seven short-term ( 4 - 8 weeks ) and one long-term ( up to 1 year ) trials comparing reboxetine with placebo , imipramine , desipramine or fluoxetine . The tolerability of reboxetine was evaluated in 2613 patients with major depression or dysthymia . Data from 1959 patients with major depressive disorder were included to assess drug efficacy . Efficacy was principally assessed using the Hamilton Depression Rating Scale ( HAM-D ) . RESULTS : Reboxetine was more effective than placebo in three of four short-term trials , and it was as effective as fluoxetine , imipramine and desipramine . In long-term treatment , reboxetine was more effective than placebo in preventing relapse ( S 50 % increase in HAM-D ) and recurrence ( HAM-D total score h 10 ) . In a subset of severely depressed patients , reboxetine was as effective as imipramine and significantly more effective than fluoxetine . Reboxetine was as effective as imipramine in the elderly , but better tolerated . The most common adverse events among the 1503 patients ( adults and elderly ) who received reboxetine were dry mouth ( 22 % ) , constipation ( 15 % ) , sweating ( 12 % ) and insomnia ( 11 % ) . Overall , reboxetine was well tolerated , as well as the SSRI fluoxetine and better than the TCAs imipramine and desipramine . CONCLUSIONS : Reboxetine is effective and well tolerated in the short and long-term treatment of depression . It is as well tolerated as fluoxetine and better than imipramine and desipramine . ( Int J Psych Clin Pract 2000 ; 4 : 201 - 208 OBJECTIVE Psychomotor disturbances can frequently be found in depressed patients and may have an important influence on the ability to drive . Additionally , effects of sedation , as seen with some antidepressants , probably impair driving performance . The present study was design ed to evaluate the effects of antidepressant monotherapy on psychomotor functions related to car-driving skills in depressive patients in a routine clinical setting . METHOD In patients ( N = 100 ) who met the ICD-10 and DSM-IV criteria for major depressive disorder were tested under steady-state plasma level conditions prior to being discharged to out-patient treatment . The study ran from January 2004 through March 2005 . All patients participated voluntarily and gave informed consent . According to the German guidelines for road and traffic safety , data were collected with the computerized Act & React Testsystem ART-90 and the Wiener Testsystem , measuring visual perception , reaction time , selective attention , vigilance , and stress tolerance . Psychopathologic symptoms were rated with the Hamilton Rating Scale for Depression . RESULTS Before discharge to outpatient treatment , 24 % of the patients tested were without clinical ly relevant psychomotor disturbances . In 60 % of the cases , mild to moderate impairments could be seen , and about 16 % of the patients were considered as severely impaired in psychomotor functions related to car-driving abilities . Data show that patients treated with selective serotonin reuptake inhibitors ( SSRIs ) or the noradrenergic and specific serotonergic antidepressant ( NaSSA ) mirtazapine had an altogether better test performance in comparison with patients receiving tricyclic antidepressants ( TCAs ) . Differences were most pronounced in measures of reactivity , stress tolerance , and selective attention . Statistically significant differences between patients treated with TCAs or the serotonin-norepinephrine reuptake inhibitor ( SNRI ) venlafaxine could not be found . Among the newer antidepressants there is an advantage for patients treated with mirtazapine , especially in tasks with high multi-channel perception and output dem and s. CONCLUSION About 16 % of depressive patients discharged from hospital to outpatient treatment must be considered unfit to drive . In 60 % of the cases , patients performed at a question able level of fitness for driving , and it seems justified to counsel patients individually , taking into account compensational factors . Data point to an advantage for patients treated with SSRIs or mirtazapine when compared with TCAs or venlafaxine . However , causal relationships can not be drawn from our data Objective : To examine the antidepressant efficacy of a dual-acting antidepressant ( mirtazapine ) in patients with post-myocardial infa rct ion ( MI ) depressive disorder . Antidepressants used in post MI trials with a r and omized , double-blind , placebo-controlled design have been restricted to selective serotonin reuptake inhibitors ( SSRIs ) . Antidepressant effects have been limited . Methods : In a prospect i ve multicenter study , 2177 patients with MI were evaluated for depressive disorder during the first year post MI . Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( DSM-IV ) criteria for major or minor depressive disorder were r and omized to a 24-week , double-blind , placebo-controlled trial . Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach , with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale ( Ham-D ) , and secondary outcomes the Beck Depression Inventory ( BDI ) and depression subscale of the Symptom Check List 90 items ( dSCL-90 ) as well as the Clinical Global Impression ( CGI ) scale . Results : Using the “ last observation carried forward ” ( LOCF ) method , mirtazapine did not show to be superior to placebo on the Ham-D , but did on the BDI , dSCL-90 , and CGI scale over the acute treatment phase of 8 weeks ( n = 91 ) . Using mixed models analysis over the entire 24 weeks of treatment ( n = 40 ) , we did find a significant difference favoring mirtazapine to placebo on the Ham-D , BDI , and CGI , but on the dSCL-90 , this difference was not significant . Conclusions : This trial shows efficacy of mirtazapine on primary and secondary depression measures . Mirtazapine seems to be safe in the treatment of post-MI depression . MI = myocardial infa rct ion ; RCT = r and omized controlled trial ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders ; CAD = coronary artery disease ; SSRI = selective serotonin reuptake inhibitors ; TCA = tricyclic antidepressant ; Ham-D = Hamilton-Depression Rating Scale ; BDI = Beck Depression Inventory ; CGI = Clinical Global Impression ; dSCL-90 = Symptom Check List 90 items , depression subscale ; SES = st and ardized effect size OBJECTIVE The authors examined gender differences in treatment response to sertraline , a selective serotonin reuptake inhibitor ( SSRI ) , and to imipramine , a tricyclic antidepressant , in chronic depression . METHOD A total of 235 male and 400 female out patients with DSM-III-R chronic major depression or double depression ( i.e. , major depression superimposed on dysthymia ) were r and omly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout . RESULTS Women were significantly more likely to show a favorable response to sertraline than to imipramine , and men were significantly more likely to show a favorable response to imipramine than to sertraline . Gender and type of medication were also significantly related to dropout rates ; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study . Gender differences in time to response were seen with imipramine , with women responding significantly more slowly than men . Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications . CONCLUSIONS Men and women with chronic depression show differential responsivity to and tolerability of SSRIs and tricyclic antidepressants .  The differing response rates between the drug classes in women was observed primarily in premenopausal women . Thus , female sex hormones may enhance response to SSRIs or inhibit response to tricyclics . Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient OBJECTIVE To determine the relative cost-effectiveness of three classes of antidepressants : tricyclic antidepressants ( TCAs ) , selective serotonin reuptake inhibitors ( SSRIs ) , and the modified TCA lofepramine , as first choice treatments for depression in primary care . DESIGN Open , pragmatic , controlled trial with three r and omised arms and one preference arm . Patients were followed up for 12 months . SETTING UK primary care : 73 practice s in urban and rural areas in Engl and . PARTICIPANTS Patients with a new episode of depressive illness according to GP diagnosis . INTERVENTIONS Patients were r and omised to receive a TCA ( amitriptyline , dothiepin or imipramine ) , an SSRI ( fluoxetine , sertraline or paroxetine ) or lofepramine . Patients or GPs were able to choose an alternative treatment if preferred . MAIN OUTCOME MEASURES At baseline the Clinical Interview Schedule , Revised ( CIS-R PROQSY computerised version ) was administered to establish symptom profiles . Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression ( HAD-D ) , CIS-R , EuroQol ( EQ-5D ) for quality of life , Short Form ( SF-36 ) for generic health status , and patient and practice records of use of health and social services . The primary effectiveness outcome was the number of depression-free weeks ( HAD-D less than 8 , with interpolation of intervening values ) and the primary cost outcome total direct NHS costs . Quality -adjusted life-years ( QALYs ) were used as the outcome measure in a secondary analysis . Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed . Estimates were bootstrapped with 5000 replications . RESULTS In total , 327 patients were r and omised . Follow-up rates were 68 % at 3 months and 52 % at 1 year . Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients r and omised to TCAs entered the preference arm than those allocated to the other choices . Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm . There were no significant differences between arms in mean cost per depression-free week . For values placed on an additional QALY of over 5000 pounds , treatment with SSRIs was likely to be the most cost-effective strategy .  TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively , but these differences were relatively modest . CONCLUSIONS When comparing the different treatment options , no significant differences were found in outcomes or costs within the sample , but when outcomes and costs were analysed together , the result ing cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option , although the probability of this did not rise above 0.6 . Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks . Further research is still needed on the management of depressive illness in primary care . This should address areas such as the optimum severity threshold at which medication should be used ; the feasibility and effectiveness of adopting structured depression management programmes in the UK context ; the importance of factors such as physical co-morbidity and recent life events in GPs ' prescribing decisions ; alternative ways of collecting data ; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early INTRODUCTION Fluoxetine , a selective serotonin reuptake inhibitor ( SSRI ) , and trimipramine , a tricyclic antidepressant ( TCA ) , were compared in terms of efficacy and tolerability in a six-week , parallel group , double-blind pilot study in 41 geriatric patients with major depression ( 61 - 85 years old ) . METHOD The Hamilton Rating Scale for Depression ( HAMD-17 ) , the Montgomery-Asberg Rating Scale ( MADRS ) , the Adjective Mood Scale ( Bf-S ) , the Clinical Global Impression ( CGI ) , and the Patients Global Impression ( PGI ) were used to measure changes in depressive symptoms . RESULTS Improvement with treatment was found on all scales . Efficacy and tolerability were similar in both groups . No statistically significant differences were found . CONCLUSION These findings suggest that fluoxetine and trimipramine are comparable in terms of efficacy and tolerability in the treatment of major depression in geriatric patients In the context of chronic physical illness , such as breast cancer , depression is associated with increased morbidity , longer periods of hospitalization , and greater overall disability . Prompt diagnosis and effective treatment is , therefore , essential . Several small studies have established the efficacy of tricyclic antidepressants ( TCAs ) in this setting , and the selective serotonin reuptake inhibitors ( SSRIs ) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile . This was a multicenter , double-blind , parallel-group study in which 179 women with breast cancer were r and omized to treatment with either the SSRI paroxetine ( 20–40mg/day ) , or the TCA , amitriptyline ( 75–150mg/day ) . After 8-weeks treatment , depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale . Clinical global impression ( CGI ) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint ; a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale . A steady improvement in quality of life was also observed in both groups . There were no clinical ly significant differences between the groups . In total , 47 ( 53.4 % ) patients in the paroxetine group and 53 ( 59.6 % ) patients in the amitriptyline group had adverse experiences , the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy . Anticholinergic effects were almost twice as frequent in the amitriptyline group ( 19.1 % ) compared with paroxetine ( 11.4 % ) . This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram , in the treatment of major depressive disorder ( MDD ) . In total , 357 out patients with MDD were r and omized to treatment with reboxetine 8 - 10 mg or citalopram 20 - 40 mg per day during 24 weeks . Primary end-point was change from baseline in the Hamilton Depression Rating Scale ( HAM-D , 21 items ) . Sexual function/dysfunction was measured by the Sexual Function scale ( SF ) . Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores : reboxetine with -21.4 and citalopram with -22.1 points ( NS ) . LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine ( -19.6 vs. -17.8 ; P = 0.034 ) . The response rate was 90.3 % for reboxetine and 92.7 % for citalopram ( NS ) . The most common side effect in the reboxetine group was dry mouth , and in the citalopram group sexual dysfunction . At week 24 , anorgasmia was reported by 5.9 % of the sexually active women in the reboxetine group vs 39 % in the citalopram group . The  dropout number  was 91 in the  reboxetine group , and 54 in the citalopram group . To summarize , both treatments gave a satisfactory antidepressant effect . The side effect profile differed between the groups , with a notably high prevalence of sexual dysfunctions in the citalopram group . The high number of dropouts in the reboxetine group , is considered as a result of the non-titration starting dose of 8 mg reboxetine per day , which gave a high incidence of early side-effects .  Depressive disorders including major depression ( MDD ) is very common , with a lifetime prevalence of at least 15 % in men and 25 % in women.1,2 Depression can be treated effectively by a range of antidepressant agents . Recent review s have suggested that the selective serotonin reuptake inhibitors ( SSRIs ) offer equal efficacy to the older antidepressant agents , such as tricyclic antidepressants , with the advantage of greater tolerability.3 - 5 Other review ers have reported that non-SSRI antidepressants , such as clomipramine , have been found to be significantly more effective than fluoxetine for the treatment of patients with severe depression.6  Reboxetine ( reboxetine mesylate , Edronax ; Pfizer , New York ) is a highly selective noradrenaline reuptake inhibitor , and the efficacy of reboxetine has been independently demonstrated in multiple r and omized , double-blind , placebo-controlled studies .7 - 9 In addition to improvements in depressive symptoms , treatment-associated improvements in social behavior ( measured using the Social Adaptation Self-evaluation Scale [SASS]),10 were noticed in one of these studies .8 In this study , reboxetine was statistically and clinical ly superior to both placebo and fluoxetine in improving social functioning . The primary objective of the current study was to assess efficacy and tolerability of reboxetine  in comparison with those of citalopram ( Cipramil ; H. Lundbeck , Copenhagen , Denmark ) in patients with MDD .  Citalopram is a highly SSRI . The antidepressant mechanism is presumed to be a result of stimulation of serotonergic neurotransmission in the central nervous system as a consequence of higher serotonin levels result ing from inhibition of the serotonin transporter . The therapeutic efficacy of citalopram in patients with MDD has been investigated in several placebo-controlled studies and in long-term and extension studies .11 The underlying rationale for this comparison was to study 2 different drug profiles , 1 drug being pure " adrenergic " and the other pure " serotonergic . " A secondary objective was to analyze the correlation between the types of depression ( ie , degree of melancholia and the efficacy of the 2 drugs ) Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors ( SSRIs ) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity . The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan ( 200 mg , L-5-HTP ; PO)–induced increases in plasma cortisol and prolactin ( PRL ) concentrations were studied in patients with major depression or obsessive compulsive disorder ( OCD ) . Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD . The  L-5-HTP – induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients . The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP . The L-5-HTP – induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different . The results suggest that fluoxetine , but not tricyclic antidepressants , potentiates 5-HT receptor – mediated stimulation of cortisol and PRL secretion in humans , consistent with available evidence that fluoxetine treatment , but not tricyclic antidepressants , increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism Selective serotonin-reuptake inhibitors ( SSRIs ) and tricyclic antidepressants ( TCAs ) have been reported to induce extrapyramidal signs and symptoms ( EPS ) . The authors examined the change from baseline EPS , measured by an objective rating scale , in a group of elderly depressed patients participating in an ongoing r and omized , double-blind comparison of nortriptyline and paroxetine .  Mild baseline EPS were present in both groups . After 6 weeks of antidepressant treatment , patients in the nortriptyline group showed a significant decrease in total EPS scores . Patients in the paroxetine group showed a similar decrease in EPS from baseline , which did not reach statistical significance . There was no significant difference between nortriptyline and paroxetine in the change in EPS BACKGROUND Selective serotonin reuptake inhibitors ( SSRIs ) and venlafaxine have been regarded as less toxic in overdose than tricyclic antidepressants ( TCAs ) . Within the TCAs , dothiepin has greater toxicity . Venlafaxine may be more toxic than SSRIs . AIM To assess the toxicity in overdose of venlafaxine and SSRIs compared to TCAs , and of dothiepin compared to other TCAs . DESIGN Cohort study of prospect ively collected data from the Hunter area , NSW , Australia . METHODS First admissions with antidepressant deliberate self-poisoning ( DSP ) ( November 1994 to April 2000 ) were identified ; the presence of seizures , life-threatening arrhythmias , coma , serotonin toxicity or ICU admission , and QRS duration were noted . RESULTS There were 538 admissions , with no deaths . The odds ratio ( OR ) for seizures with dothiepin vs. other TCAs was 3.4 ( 95%CI 1.2 - 9.9 ) . Seizures occurred in 7/51 ( 14 % ) venlafaxine overdoses ; all patients with seizures consumed > or = 900 mg . The OR for seizures vs. TCAs was 4.4 ( 95%CI 1.4 - 13.8 ) . Coma was less likely with venlafaxine and SSRIs . SSRIs , but not venlafaxine , were less likely to prolong the QRS to > or = 100 ms . ICU admission was less likely for SSRIs . Serotonin toxicity was much more common with venlafaxine and SSRIs . DISCUSSION Venlafaxine and dothiepin are pro-convulsant in overdose . Venlafaxine is more likely to cause serotonin toxicity , but less likely to cause coma than TCAs . SSRIs are less likely to cause coma , require ICU admission , or prolong the QRS , but are more likely to cause serotonin toxicity . Antidepressants other than TCAs or venlafaxine should be considered in patients at risk of seizure or suicide Abstract Objectives . Evidence in favour of switching between selective serotonin reuptake inhibitor ( SSRI ) and tricyclic ( TCA ) antidepressants in treatment resistant depression has been tested in a few studies only , consequently a prospect i ve study was undertaken to evaluate the impact of switching strategies . Methods . One hundred eighty-nine patients who failed to respond to a previous antidepressant were r and omised to four arms : firstly they received citalopram or desipramine for a 4-week period ; secondly , those who failed to respond were treated for a further 4-week period with the same antidepressant ( citalopram-citalopram and desipramine-desipramine arms ) or switched to the alternate one ( citalopram-desipramine and desipramine-citalopram arms ) . Results . There was no difference in the first 4-week phase between patients receiving citalopram versus desipramine in Hamilton Rating Scale for Depression ( HRSD ) , Montgomery – Asberg Depression Rating Scale ( MADRS ) , and Clinical Global Impression ( CGI ) scores . In the second 4-week phase remitter rates were higher among non-switched patients ( P = 0.04 ) . Moreover , considering HRSD and MADRS , switched patients reported significantly higher scores ( P ≤ 0.02 for both scales at each time-point ) . Conclusions . This study supports the thesis that switching from an SSRI to a TCA ( and vice versa ) in non-responders to a 4-week trial of an SSRI/TCA is not associated with improved response . The result goes in the opposite direction to that predicted by current guidelines Background : Parkinson disease ( PD ) is a common neurodegenerative disease affecting up to 1 million individuals in the United States . Depression affects up to 50 % of these patients and is associated with a variety of poor outcomes for patients and their families . Despite this , there are few evidence -based data to guide clinical care . Methods : An NIH-funded , r and omized , controlled trial of paroxetine CR , nortriptyline , and placebo in 52 patients with PD and depression . The primary outcomes were the change in the Hamilton Depression Rating Scale ( HAM-D ) and the percentage of depression responders at 8 weeks . Results : Nortriptyline was superior to placebo for the change in HAM-D ( p < 0.002 ) ; paroxetine CR was not . There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks ( p < 0.079 ) . Response rates favored nortriptyline ( p = 0.024 ) : nortriptyline 53 % , paroxetine CR 11 % , placebo 24 % . In planned contrasts of response rates , nortriptyline was superior to paroxetine CR ( p = 0.034 ) . Nortriptyline was also superior to placebo in many of the secondary outcomes , including sleep , anxiety , and social functioning , while paroxetine CR was not . Both active drug treatments were well tolerated . Conclusions : Though relatively modest in size , this is the largest placebo-controlled trial done to date in patients with Parkinson disease ( PD ) and depression .  Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not . When compared directly , nortriptyline produced significantly more responders than did paroxetine CR . The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors . ARR = absolute risk reduction ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , 4th edition ; HAM-A = Hamilton Anxiety Scale ; HAM-D = Hamilton Depression Rating Scale ; MMSE = Mini-Mental State Examination ; NNT = number needed to treat ; PD = Parkinson disease ; PDQ = Parkinson ’s Disease Question naire ; PSQI = Pittsburgh Sleep Quality Index ; SCID = Structured Clinical Interview ; SSRI = selective serotonin reuptake inhibitor ; TCA = tricyclic antidepressant ; UPDRS = Unified Parkinson ’s Disease Rating Scale OBJECTIVES : Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache , only few studies have investigated the efficacy of this treatment and the results are contradictory . In addition , the new selective serotonin reuptake inhibiting antidepressants , which are widely used in depression and of potential value in pain management , have never been investigated in a placebo controlled study of tension-type headache . The aim was to evaluate the efficacy of amitriptyline and of the selective serotonin reuptake inhibitor citalopram in chronic tension-type headache . METHODS : Forty non-depressed patients with chronic tension type headache were included in a 32 week , double blind , placebo controlled , three-way crossover study . RESULTS : Thirty four patients completed the trial .  Amitriptyline reduced area under the headache curve by 30 % compared with placebo ( P = 0.002 ) , whereas citalopram had no significant effect ( P = 0.68 ) . Explanatory analyses showed that amitriptyline significantly reduced the duration of headache ( P = 0.01 ) , headache frequency ( P = 0.01 ) , and intake of analgesics ( P = 0.02 ) but not headache intensity ( P = 0.12 ) . CONCLUSION : Although amitriptyline did not eliminate the headache , it provided a clinical ly important reduction of headache in the majority of otherwise treatment resistant patients . The differential effect of amitriptyline and citalopram indicates that mechanisms other than inhibition of serotonin reuptake are involved in the analgesic effect of the tricyclic antidepressants . Amitriptyline , but not citalopram , is valuable in the prophylactic treatment of chronic tension type headache BACKGROUND Patients with depression have higher rates of cardiac morbidity and mortality . Alterations of cardiac autonomic functions associated with depression may partly explain this . Prospect i ve studies comparing the effects of antidepressants on these abnormalities are limited due to confounding factors and co-morbidities . METHODS Cardiac autonomic functions were studied in  antidepressant naïve patients with major depression ( without co-morbid medical or psychiatric disorders ) before and after treatment with repetitive transcranial magnetic stimulation ( rTMS ; n=30 ) , specific serotonin reuptake inhibitors ( SSRIs ; n=32 ) and tricyclic antidepressants ( TCAs ; n=32 ) . Conventional autonomic function tests and time- and frequency-domain measures of heart rate variability ( HRV ) were measured using st and ard procedures . Changes in autonomic functions were compared across the three treatment groups using repeated measures analysis of variance ( ANOVA ) using sex and age as covariates . RESULTS Depression improved by comparable extent across patients treated with the three treatments . Overall , there was no change in cardiac autonomic functions . However , significant group × occasion interactions were noted for HRV measures . Both time- and frequency-domain HRV measures showed increase with rTMS and decrease with TCAs ; they remained virtually unchanged with SSRIs . LIMITATIONS One of the major limitations of our work being we could not r and omize the treatment groups . CONCLUSIONS The effects of antidepressant treatments on cardiac autonomic function abnormalities found in depression vary with the mode of treatment used . Long-term clinical implication s of these effects on cardiac health of patients with depression need further studies Efficacy Although clinicians often view MAOIs as more difficult to prescribe than agents in other classes , there is little doubt about their efficacy . In bipolar depression , for example ( where impactful treatments are few and far between ) , response rates with tranylcypromine have been reported to exceed 80 % , and this agent may be more efficacious than TCAs such as imipramine , particularly in patients with anergic , motor-retarded features.4 MAOIs also may yield better antidepressant efficacy than TCAs in chronic depression and dysthymia.5 In refractory major depression , response rates of at least 40%–50 % have been reported for both tranylcypromine and phenelzine , with comparable head-to-head efficacy.6 It was therefore surprising that , in the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) trials , patients r and omly assigned to tranylcypromine ( a fourth-level intervention following nonresponse to an SSRI and 2 other interventions ) obtained a meager 6.9 % remission rate.7 However , low mean dosing of tranylcypromine in that study ( < 40 mg/d ) quite likely underestimated optimal MAOI benefits for advanced forms of treatment-resistant depression . Studies from the 1970s and 1980s made MAOIs virtually synonymous with treatment for atypical depression , with reports of superiority to TCAs ( review ed by Henkel et al8 ) . MAOIs are also often thought of for anxious depression on the basis of an older literature comparing phenelzine with tricyclics such as amitriptyline.9,10 Much of this literature focused on pre – DSM-III constructs such as “ neurotic ” or “ reactive ” depressions that may also relate to atypical depression . Excitement surrounding such apparent differential therapeutics was largely dissipated by the rapid ascension of SSRIs , which essentially replaced TCAs as the antidepressants of first choice by the early 1990s . Whereas MAOIs were clearly superior to TCAs , there was little reason to view them as superior to SSRIs , which were substantially safer BACKGROUND An estimated 30 % to 40 % of patients with depression do not sufficiently respond to treatment with selective serotonin reuptake inhibitors ( SSRIs ) and the period in which treatment efficacy can be assessed is relatively long . Therefore , a test to identify potential nonresponders could be useful in the treatment of depression . Serotonin transporter gene ( SLC6A4 ) variations have been reported to account for differences in the way individuals respond to SSRI treatment . OBJECTIVE A decision-analytic model was used to assess whether pretreatment genetic testing for 5-HTTLPR , a polymorphism of the SLC6A4 genotype , could be an efficient tool in the treatment of depression . METHODS A theoretical clinical decision-analytic model was constructed to compare the current treatment strategy in The Netherl and s with an alternative strategy for the treatment of depression . Under treatment guidelines in The Netherl and s , all patients with depression receive SSRI treatment ( nontesting strategy ) . Under the alternative strategy , genetic testing would be performed to identify which class of antidepressant would be the best choice for initiation of treatment ( genetic testing strategy ) . Probabilities ( predicted results ) for this model were based on data from previous studies and the opinions of experts in the field of psychopharmacology . To test the robustness of the model , 6- and 12-week remission rates for patients treated with SSRIs were varied in a sensitivity analysis using a predetermined range that was established based on expert opinion . Threshold analyses were performed on the parameters of serotonin transporter genotype frequency and response and nonresponse rates for patients receiving SSRIs , serotonin-norepinephrine reuptake inhibitors ( SNRIs ) , and tricyclic antidepressants ( TCAs ) to determine the value for a variable at which it could be concluded that a change in treatment strategy would be preferred . RESULTS When genetic testing was performed before an antidepressant was prescribed , 64.6 % of patients were predicted to be in remission after 6 weeks of treatment compared with 60.0 % of patients who did not receive genetic testing . After 12 weeks , 79.5 % of patients in the testing group who received an SNRI as initial treatment and 83.2 % of those who received a TCA initially were predicted to be in remission compared with 76.7 % of patients in the nontesting group . Sensitivity analyses indicated that the model was robust to variation of probability estimates within their plausible ranges . However , these findings were based on a theoretic model and did not include cost assessment . Pretreatment genetic testing must be evaluated further in r and omized clinical trials and costs must be assessed before implementing this strategy in routine psychiatric practice can be recommended . CONCLUSIONS The findings of this study suggest that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment BACKGROUND Antidepressants are commonly prescribed medications , but their effect on cardiovascular morbidity and mortality remains unclear . METHODS Prospect i ve cohort study of 136 293 community-dwelling postmenopausal women in the Women 's Health Initiative ( WHI ) . Women taking no antidepressants at study entry and who had at least 1 follow-up visit were included . Cardiovascular morbidity and all-cause mortality for women with new antidepressant use at follow-up ( n = 5496 ) were compared with those characteristics for women taking no antidepressants at follow-up ( mean follow-up , 5.9 years ) . RESULTS Antidepressant use was not associated with coronary heart disease ( CHD ) .  Selective serotonin reuptake inhibitor ( SSRI ) use was associated with increased stroke risk ( hazard ratio [HR],1.45 , [ 95 % CI , 1.08 - 1.97 ] ) and all-cause mortality ( HR,1.32 [ 95 % CI , 1.10 - 1.59 ] ) . Annualized rates per 1000 person-years of stroke with no antidepressant use and SSRI use were 2.99 and 4.16 , respectively , and death rates were 7.79 and 12.77 . Tricyclic antidepressant ( TCA ) use was associated with increased risk of all-cause mortality ( HR,1.67 [ 95 % CI , 1.33 - 2.09 ] ; annualized rate , 14.14 deaths per 1000 person-years ) . There were no significant differences between SSRI and TCA use in risk of any outcomes . In analyses by stroke type , SSRI use was associated with incident hemorrhagic stroke ( HR , 2.12 [ 95 % CI , 1.10 - 4.07 ] ) and fatal stroke ( HR , 2.10 [ 95 % CI , 1.15 - 3.81 ] ) . CONCLUSIONS In postmenopausal women , there were no significant differences between SSRI and TCA use in risk of CHD , stroke , or mortality . Antidepressants were not associated with risk of CHD .  Tricyclic antidepressants and SSRIs may be associated with increased risk of mortality , and SSRIs with increased risk of hemorrhagic and fatal stroke , although absolute event risks are low . These findings must be weighed against quality of life and established risks of cardiovascular disease and mortality associated with untreated depression The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants ( TCAs ) , and the frequency and type of adverse events , have made the treatment of depression in this group difficult . The selective serotonin reuptake inhibitors ( SSRIs ) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs . We compared the therapeutic actions and side effects produced by citalopram , the most selective SSRI available , with amitriptyline in a group of elderly patients ( aged 65 and older ) diagnosed with major depression . In a double-blind , double-dummy , parallel-group , multicenter comparison of citalopram ( 20 or 40 mg/day ) and amitriptyline ( 50 or 100 mg/day ) , patients who did not respond to placebo during a 1-week single-blind phase were r and omly assigned to receive citalopram or amitriptyline for 8 weeks . Efficacy measures included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Depression Scale ( HAMD ) , and Clinical Global Impressions . Both drug treatments produced equivalent time-related declines in severity of depression , so that by 8 weeks slightly more than 50 % of the patients in each group experienced marked recovery , defined as MADRS scores < or = 12 . Amitriptyline produced a greater overall incidence of adverse events , including a significantly higher ( P < 0.001 ) percentage of patients reporting dry mouth ( 34 % vs. 7 % ) , as well as a significantly higher ( P < 0.02 ) incidence of somnolence . Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group . For only one event ( nausea ) did the citalopram group report a significantly greater ( P = 0.012 ) incidence ( 12.8 % vs. 4.8 % ) . On the basis of these results , it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly . Because of its low incidence and low magnitude of side effects , citalopram seems especially useful in private practice
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
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 .