A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial. (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD). Monoamine oxidase inhibitors revisited: what you should know. Forms of atypical depression and their response to antidepressant drugs Combination of inositol and serotonin reuptake inhibitors in the treatment of depression Treatment of endogenous depressions resistant to tricyclic antidepressants or related drugs by lithium addition. Results of a placebo-controlled double-blind study. Citalopram versus desipramine in treatment resistant depression: Effect of continuation or switching strategies. A randomized open study The impact of chronic depression on acute and long-term outcomes in a randomized trial comparing selective serotonin reuptake inhibitor monotherapy versus each of 2 different antidepressant medication combinations. Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients. A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Using non-steroidal anti-inflammatory drugs in the treatment of depression. The efficacy of drugs and psychotherapy in the treatment of acute depressive episodes. Fluoxetine versus trimipramine in the treatment of depression in geriatric patients. Antidepressants and driving ability: results from a clinical study.
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 This comprehensive study investigated both the role of antidepressant drugs in the treatment of affective disorders of later life and their safety with careful clinical and pharmacological monitoring . A 7-week double-blind comparison was made of the efficacy and safety of nortriptyline ( a tricyclic ) , phenelzine ( a monoamine oxidase inhibitor ) , and placebo . The results indicated a response rate of approximately 60 % for both nortriptyline and phenelzine versus a 13 % response rate for placebo .  Anticholinergic side effects were more frequently reported in the nortriptyline group . Orthostatic symptoms were reported with similar frequency in both drug groups . Overall , both drugs were well tolerated 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 Major Depressive Disorder ( MDD ) is a common illness that affects > 40 million people worldwide , and antidepressants are one of the top 5 leading classes of pharmaceuticals with annual sales in excess of $ 20 billion ( 1,2 ) . The current st and ard of care focuses on serotonin−norepinephrine reuptake inhibitors ( SNRI ) and selective serotonin reuptake inhibitors ( SSRI ) ; however , patients often respond poorly . In fact , the National Institute of Mental Health conducted a large-scale STAR*D study and found that 63 % of patients did not achieve remission with the SSRI Citalopram ( 1,3−5 ) . Citalopram was originally developed in Lundbeck in the late 1980s and sold as a racemate . Lundbeck , in collaboration with Forest Laboratories , has recently released an up date d version called Escitalopram ( also known as Lexapro ) , which is the single (S)-enantiomer of the racemic Citalopram , which provided new patent life . In 2009 , Lexapro garnered ∼$2.7 billion in sales in the US ( Figure ​(Figure1)1 ) ( 2 ) . Figure 1 Structures of Citalopram , Escitalopram , and TC-5214 . An alternative hypothesis for depression emerged over 30 years ago and suggests that a cholinergic imbalance ( hypercholinergic tone ) is a major factor in depression , and both clinical and pre clinical studies have implicated neuronal nicotinic cholinergic receptors ( NNRs ) rather than muscarinic receptors ( 5 ) . On the basis of these data , AstraZeneca and Targacept have explored the role of NNR antagonism in depressive disorders and recently announced the initiation of a phase III trial of TC-5214 , (S)-(+)-mecamylamine , as an adjunct therapy with Citalopram . TC-5214 is a low molecular weight ( 167.3 as free base , 203.8 as the HCl salt ) , basic ( pKa = 11.5 ) compound , freely soluble in water . While TC-5214 displays modest selectivity among the NNRs , its antidepressive properties are presumed to be the result of inhibition of the α4β2 NNRs . Pre clinical ly , TC-5214 demonstrated robust efficacy in rodent models of depression ( forced swim and behavioral despair ) and anxiety ( social interaction and light/dark chamber ) . The (S)-enantiomer showed a superior preclincial safety profile compared to that of either the racemic compound or the (R)-enantiomer . Furthermore , TC-5214 was well tolerated in both acute and chronic toxicity tests , displayed no mutagenic potential , and possessed pharmacokinetic properties suitable for development ( 3−5 ) . In 2009 , Targacept conducted a double blind , placebo controlled phase IIb trial in MMD patients with TC-5214  , as an adjunct treatment with Citalopram demonstrated superiority to placebo in both primary and secondary outcome measures ( 3−5 ) . This positive outcome led to a license agreement in December of 2009 with AstraZeneca for the global development and commercialization of TC-5214 . On June 23 , 2010 , AstraZeneca and Targacept announced the enrollment of the first patients in the phase III trial of TC-4214 . Coined the Renaissance Program , the trial will include two fixed dose and two flexible dose phase III studies of TC-5214 as an adjunct treatment for patients with poor response to st and ard SSRI or SNRI therapy . Each fixed dose and flexible dose phase III study will employ an initial open label phase wherein patients diagnosed with MDD receive one of seven marketed SSRIs or SNRIs for eight weeks to assess therapeutic response . Patients that respond poorly will then be r and omized into a double blind , placebo controlled second phase to receive a fixed or a flexible dose of TC-5214 or placebo , twice daily , while continuing the SSRI or SNRI therapy . A change from double blind baseline for TC-5214 on the Montgomery−Asberg Depression Rating Scale ( MADRS ) as compared to placebo is the primary outcome measure . The program will also include a double blind , placebo controlled study for long-term safety . The companies plan completion of the trial in time to file an IND with the FDA in late 2012 ( 3−5 ) . MMD is the leading cause of disability in the US for people 15−44 , and the burden for MDD in the US in 2000 was in excess of $ 83 billion ( 6 ) . When broken down , the workplace burden for lost time is ∼62 % , treatment costs account for ∼31 % , and suicide related costs average 7 % ( 6 ) . For those suffering from MDD with poor response to SSRIs and SNRIs , the phase III data is anxiously awaited 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 Three definitions of atypical depression are evaluated with respect to the effects of monoamine oxidase inhibitors ( MAOIs ) and tricyclic antidepressants ( TCAs ) on the basis of pooled data from several double-blind studies . Those three definitions of atypical depression are depression with associated panic , depression secondary to a diagnosis of anxiety , and depression with reversed vegetative change . In none of these forms was a drug difference observed . However , when gender was taken into account , MAOIs were superior to TCAs in depressed women with panic attacks , whereas TCAs were superior to MAOIs in depressed men with panic attacks 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 The therapeutic efficacy of lithium added to tricyclic antidepressants ( TCA ) or related thymoleptics was investigated in 27 endogenous depressive patients responding unsatisfactorily to these drugs alone . All patients received lithium during two weeks , however , with a delay of one week in 13 of them , the attribution to active treatment or placebo for the first seven days being double-blind . A statistically significant improvement compared to placebo occurred after lithium addition . The results of the double-blind part of the study as well as the observations during the total two-week period suggest that endogenous depression failing to respond to thymoleptic drug treatment can be improved within a short time by the co-administration of the two treatments in the indicated sequence . However , the proportion of patients improved and the rapidity of improvement noted in this study were less favorable than reported by the investigators who discovered the therapeutic principle 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 OBJECTIVE To compare sociodemographic and clinical features , acute and continuation treatment outcomes , and adverse events/side effect burden between out patients with chronic ( current episode > 2 years ) versus nonchronic major depressive disorder ( MDD ) who were treated with combination antidepressant therapy or selective serotonin reuptake inhibitor ( SSRI ) monotherapy . METHOD 663 out patients with chronic ( n = 368 ) or nonchronic ( n = 295 ) moderate to severe DSM-IV-TR MDD ( 17-item Hamilton Depression Rating Scale score ≥ 16 ) were enrolled from March 2008 through September 2009 in a single-blind 7-month prospect i ve r and omized trial conducted at 6 primary and 9 psychiatric care sites across the United States . Participants were treated with escitalopram monotherapy plus placebo or 1 of 2 combination treatments ( bupropion sustained-release [ SR ] + escitalopram or venlafaxine extended-release [ XR ] + mirtazapine ) . Analyses compared baseline sociodemographic and clinical characteristics , rates of remission ( at least 1 of the last 2 consecutive scores on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report [ QIDS-SR16 ] < 6 , with the other < 8) , and adverse events/side effect burden ( Frequency , Intensity , and Burden of Side Effects Ratings ) obtained at 12 and 28 weeks . RESULTS Participants with chronic MDD were at greater socioeconomic disadvantage and had greater medical and psychiatric disease burden  . The chronic and nonchronic groups did not differ in rates of remission at 12 weeks ( 35.9 % vs 42.0 % , respectively ; odds ratio [ OR ] = 0.778 , P = .1500 ; adjusted OR [ AOR ] = 0.956 , P = .8130 ) or at 28 weeks ( 41.0 % vs 49.8 % , respectively ; OR = 0.706 , P = .0416 ; AOR = 0.837 , P = .3448 ) . Participants with chronic MDD had higher final QIDS-SR(16 ) scores and smaller overall percent changes in QIDS-SR(16 ) from baseline to exit , but these differences did not remain after adjusting for covariates . There were no significant differences in adverse events or side effect burden . No significant interactions were found between chronicity and type of treatment at 12 or 28 weeks . CONCLUSION Chronicity of illness does not appear to differentially impact acute or longer-term outcomes with SSRI monotherapy or combination antidepressant medication treatment in patients with moderate to severe nonpsychotic MDD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00590863 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 Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors ( SSRIs ) in severe major depressive disorder ( MDD ) . This prospect i ve pragmatic trial tests this hypothesis . Patients with severe MDD were r and omly assigned to either duloxetine ( a serotonin and norepinephrine-reuptake inhibitor ) or physicians ’ choice of four generic SSRIs . Nonblinded , flexibly dosed treatment was used to mimic clinical practice . To address potential investigator bias , the patient-reported Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR ) was used as the primary efficacy outcome measure . A total of 750 out patients ( 19.2 % , African descent ; 14.8 % , Hispanic ) were r and omized . The primary outcome , remission at week 12 by QIDS-SR , was numerically greater for duloxetine compared with SSRIs ( 36 vs. 32 % ) , but this difference was not statistically significant . Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item , the Brief Pain Inventory , and the Sheehan Disability Scale . Remission superiority on the QIDS-SR was not achieved . Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning . Study demographics suggest a more generalizable racial and ethnic population than is typical in r and omized clinical trials OBJECTIVE Despite the progressive increase in the number of antidepressants , many patients with major depressive disorder continue to be symptomatic . Clearly , there is an urgent need to develop better tolerated and more effective treatments for this disorder . The use of S-adenosyl methionine ( SAMe ) , a naturally occurring molecule that serves as a methyl donor in human cellular metabolism , as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development . METHOD Participants were 73 serotonin reuptake inhibitor ( SRI ) nonresponders with major depressive disorder enrolled in a 6-week , double-blind , r and omized trial of adjunctive oral SAMe ( target dose : 800 mg/twice daily ) . Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial . The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale ( HAM-D ) . RESULTS The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe ( 36.1 % and 25.8 % , respectively ) than adjunctive placebo ( 17.6 % versus 11.7 % , respectively ) . The number needed to treat for response and remission was approximately one in six and one in seven , respectively . There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason ( 20.6 % versus 29.5 % , respectively ) , due to adverse events ( 5.1 % versus 8.8 % , respectively ) , or due to inefficacy ( 5.1 % versus 11.7 % , respectively ) . CONCLUSIONS These preliminary results suggest that SAMe can be an effective , well-tolerated , and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication BACKGROUND clinicians have long noticed a correlation between physiological markers of inflammation and depression . The best-known example is the activation of the hypothalamus-pituitary-adrenal axis and cortisol secretion ; however more recent studies have demonstrated increased salivary prostagl and ins and plasma acute phase proteins in depressed patients . To date four r and omised controlled trials have used celecoxib or rofecoxib as adjuncts to serotonin selective reuptake inhibitors in the treatment of depression . These suggested a statistically significant decrease in depressive symptoms in the patients taking NSAIDs and SSRIs , compared to patients taking SSRIs alone . Interpretation of these results is limited by the small sample size and short duration of these preliminary studies . The research only considers depressed patients receiving treatment in secondary care ; no study has examined the effectiveness of NSAIDs as an adjunct in primary care , even though most cases of depression in the UK are managed in the community by general practitioners . PROPOSAL we propose a multi-centre double-blinded r and omised controlled trial with two objectives : to determine whether citalopram plus celecoxib dual therapy achieves a greater reduction in depressive symptoms ( quantified using the Hamilton Depression Rating Scale ( HDRS ) ) within four weeks , compared to citalopram monotherapy ; and to determine whether citalopram plus celecoxib dual therapy is more likely to achieve remission ( HDRS score ? 7 ) of moderate to severe depression within six months , compared with citalopram monotherapy . The endpoints will be the reduction in HDRS score after 4 weeks of treatment , and the HDRS score after 26 weeks of treatment . The study will enrol 452 participants from general practice s who have a moderate or severe , current or recurrent major depressive episode when medication with an SSRI is considered . The study population will be stratified according to age , sex , HDRS score , age of onset of first episode , number of previous depressive episodes and duration of current episode . The population will then be r and omised into two groups . Subjects will be interviewed to determine HDRS score , measure blood pressure , count pills and discuss side-effects . This will occur weekly for the first four weeks , and every four weeks thereafter The efficacy of tricyclic antidepressants and various psychotherapies , in comparison with one another or in combination , has not been fully established in r and omized clinical trials . The authors present a r and omized controlled trial comparing the combination of amitriptyline and short-term interpersonal psychotherapy , either treatment alone , and nonscheduled supportive psychotherapy in ambulatory patients with acute depression . They found that pharmacotherapy and psychotherapy alone were equally efficacious and better than nonscheduled treatment . The combination treatment of  psychotherapy and pharmacotherapy was more effective than either treatment alone and delayed the onset of symptomatic failure 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 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
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 .