title: A Randomized, Naturalistic, Parallel-Group Study for the Long-Term Treatment of Panic Disorder With Clonazepam or Paroxetine Modeling the longitudinal latent effect of pregabalin on self-reported changes in sleep disturbances in outpatients with generalized anxiety disorder managed in routine clinical practice Remission of Generalized Anxiety Disorder after 6 Months of Open-Label Treatment with Venlafaxine XR Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Collaborative Paroxetine Panic Study Investigators. Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial Genetic polymorphisms in the PACAP and PAC1 receptor genes and treatment response to venlafaxine XR in generalized anxiety disorder 2nd year maintenance and discontinuation of imipramine in panic disorder with agoraphobia. Rate of improvement during and across three treatments for panic disorder with or without agoraphobia: cognitive behavioral therapy, selective serotonin reuptake inhibitor or both combined. Maintenance drug treatment of panic disorder. I. Results of a prospective, placebo-controlled comparison of alprazolam and imipramine. Treatment-related alteration of cortisol predicts change in neuropsychological function during acute treatment of late-life anxiety disorder. Pregabalin long-term treatment and assessment of discontinuation in patients with generalized anxiety disorder. Broadening of Generalized Anxiety Disorders Definition Does not Affect the Response to Psychiatric Care: Findings from the Observational ADAN Study Three year naturalistic outcome study of panic disorder patients treated with paroxetine Time to relapse after 6 and 12 months' treatment of generalized anxiety disorder with venlafaxine extended release. Effects of once-daily extended release quetiapine fumarate on patient-reported outcomes in patients with generalized anxiety disorder Personality disorders and time to remission in generalized anxiety disorder, social phobia, and panic disorder. The Nottingham Study of Neurotic Disorder: predictors of 12-year outcome of dysthymic, panic and generalized anxiety disorder. Antipanic Drug Modulation Of 35% CO2 Hyperreactivity and Short-Term Treatment Outcome The diagnosis and treatment of generalized anxiety disorder. Agomelatine prevents relapse in generalized anxiety disorder: a 6-month randomized, double-blind, placebo-controlled discontinuation study. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial Long-term efficacy of pregabalin in generalized anxiety disorder Predictors of outcome of pharmacological and psychological treatment of late-life panic disorder with agoraphobia. Duration of Imipramine Therapy and Relapse in Panic Disorder With Agoraphobia A 15-year follow-up study of patients with panic disorder. Relation of Serotonin Transporter Genetic Variation to Efficacy of Escitalopram for Generalized Anxiety Disorder in Older Adults Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder A randomized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability A Naturalistic Long-Term Comparison Study of Selective Serotonin Reuptake Inhibitors in the Treatment of Panic Disorder Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): data from a randomized-withdrawal, placebo-controlled maintenance study. A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. Antidepressant medication augmented with cognitive-behavioral therapy for generalized anxiety disorder in older adults. Tapering Clonazepam in Patients With Panic Disorder After at Least 3 Years of Treatment
abstract: Abstract This long-term extension of an 8-week r and omized , naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam  ( n = 47 ) and paroxetine  ( n = 37 ) over a 3-year total treatment duration . Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine ( both taken at bedtime ) . This study reports data from the long-term period ( 34 months ) , following the initial 8-week treatment phase . Thus , total treatment duration was 36 months . Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine , but patients with partial primary treatment success were switched to the combination therapy . At initiation of the long-term study , the mean doses of clonazepam and paroxetine were 1.9 ( SD , 0.30 ) and 38.4 ( SD , 3.74 ) mg/d , respectively . These doses were maintained until month 36 ( clonazepam 1.9 [ SD , 0.29 ] mg/d and paroxetine 38.2 [ SD , 3.87 ] mg/d ) . Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine ( mean difference : CGI-Severity scale −3.48 vs −3.24 , respectively , P = 0.02 ; CGI-Improvement scale 1.06 vs 1.11 , respectively , P = 0.04 ) . Both treatments similarly reduced the number of panic attacks and severity of anxiety . Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine ( 28.9 % vs 70.6 % , P < 0.001 ) . The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course . There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events Background Anxiety disorders are among the most common psychiatric illnesses , with generalized anxiety disorder ( GAD ) being one of the most common . Sleep disturbances are highly prevalent in GAD patients . While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials , mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin . Thus , the objective of this study was to model the longitudinal latent effect of pregabalin or usual care ( UC ) therapies on changes in sleep in out patients with GAD under routine clinical practice . Methods Male and female GAD out patients , aged 18 years or above , from a 6-month prospect i ve noninterventional trial were analyzed . Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms ( assessed with Hamilton Anxiety Scale ) and sleep disturbances ( assessed with Medical Outcomes Study -Sleep Scale [ MOS-S ] ) were estimated by a conditional latent curve model applying structural equation modeling . Results A total of 1,546 pregabalin-naïve patients were analyzed , 984 receiving pregabalin and 562 UC .  Both symptoms of anxiety and sleep disturbances were significantly improved in both groups , with higher mean ( 95 % confidence interval ) score reductions in subjects receiving pregabalin : −15.9 ( −15.2 ; −16.6 ) vs −14.5 ( −13.5 ; −15.5 ) , P=0.027 , in Hamilton Anxiety Scale ; and −29.7 ( −28.1 ; −31.3 ) vs −24.0 ( −21.6 ; −26.4 ) , P<0.001 , in MOS-S. The conditional latent curve model showed that the pregabalin  effect on sleep disturbances was significant ( γ = −3.99 , P<0.001 ) , after discounting the effect on reduction in anxiety symptoms . A mediation model showed that 70 % of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement . Conclusion A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect , not mediated by improvements in anxiety symptoms Background : Remission has become one of the leading outcome criteria in clinical trials . Data collected by this research group assessed the rate of remission after 6 months of treatment of generalized anxiety disorder ( GAD ) with venlafaxine XR , to search for predictors of remission and to define how early on in treatment later remission can be predicted . Method : Two hundred sixty-eight patients with a GAD diagnosis enrolled into an open-label 6-month-treatment trial with venlafaxine XR ( 75 - 225 mg/day ) . Remission was defined by a Hamilton anxiety scale total score ≤7 . Logistic regression approaches were used to find out how early on in treatment later remission could be predicted , as well as to determine predictors of remission . In addition , adverse events were also followed over time . Results : While the total enrolled patient sample ( n = 268 ) had a remission rate of 53 % , 6-month completers ( n = 159 ) had a remission rate of 79 % . The only statistically significant predictor of remission , independent of baseline anxiety and depression levels , was a low Eysenck neuroticism score . The remission status outcome could best be predicted after 8 weeks of treatment when a CGI-I score of 1 or 2 predicted later remission with 78 % accuracy and later nonremission with 91 % accuracy . The incidence of adverse events decreased over the 6-month period , with sexual adverse events decreasing the least . Conclusion : The only significant predictor of remission was a low score on the Eysenck neuroticism scale . The earliest reliable prediction of later remission , based on improvement , could be made after 8 weeks of treatment with 91 % accuracy Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies . This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder . Patients who satisfactorily completed a 12-week , double-blind , placebo-controlled study of paroxetine and clomipramine  could choose to continue receiving their r and omized treatment for a further 36 weeks . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression Scale , the Hamilton Anxiety Rating Scale , the Marks Sheehan Phobia Scale and the Sheehan Disability Scale . In total , 176 patients were included in the intention-to-treat population . The number of full panic attacks decreased in all three groups during the 12-week study , and improvements continued with long-term therapy . Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks , and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks . There were no significant differences between paroxetine and clomipramine . The proportion of patients who withdrew from the study due to adverse effects  was greater in the clomipramine group ( 19 % ) than in either the paroxetine group ( 7 % ) or the placebo group ( 9 % ) . Paroxetine was significantly more effective than placebo and as effective as ( but better tolerated than ) clomipramine in the long-term treatment of panic disorder . Not only was efficacy maintained , but continued improvement was also seen , indicating the importance of long-term treatment in patients with panic disorder Variation in genes involved in serotonergic signaling is thought to be associated with antidepressant treatment response in generalized anxiety disorder ( GAD ) . We examined a possible interaction between the serotonin transporter gene ( SLC6A4 ) 5-HTTLPR/rs25531 haplotype and the serotonin 2A receptor gene ( HTR2A ) single-nucleotide polymorphism ( SNP ) rs7997012 in antidepressant treatment outcome in GAD . Patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study . Genotypes obtained for the 5-HTTLPR/rs25531 ( La/La , La/S or S/S ) haplotype and rs7997012 SNP ( G or A ) in the European American population ( n=112 ) were used for pharmacogenetic analysis . Our data show that subjects with genotypes La/La+G/G or La/La+G/A ( n=28 ) had significantly lower Hamilton Anxiety Scale ( HAM-A ) scores than those with genotypes La/S+A/A or S/S+A/A ( n=12 ) at 6 months ( HAM-A difference=10.7 ; P<0.0001 ) . Single-marker analysis only showed HAM-A differences of 4.3 ( 5-HTTLPR/rs25531 : La/La versus La/S+S/S ) and 4.8 ( rs7997012 : G/G+G/A versus A/A ) , showing for the first time a significant gene – gene interaction between these markers The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) as maintenance monotherapy for patients with generalized anxiety disorder ( GAD ) .  Time-to-event ( anxiety symptom recurrence ; maximum 52 weeks ) multicenter , r and omized-withdrawal , parallel-group , double-blind , placebo-controlled study of quetiapine XR ( 50–300 mg/day ) following open-label run-in ( 4–8 weeks ) and open-label stabilization ( ≥12 weeks ) . Primary variable : time from r and omization to anxiety event . Secondary variables included : Hamilton Anxiety Rating Scale ( HAM-A ) total , HAM-A psychic/somatic anxiety factors , Clinical Global Impression-Severity of Illness ( CGI-S ) , and Quality of Life , Enjoyment and Satisfaction Question naire ( Q-LES-Q ) scores ; adverse events ( AE ) reporting . Four hundred and thirty-two patients , stabilized on quetiapine XR , were r and omized to continue quetiapine XR ( N=216 ) or switch to placebo ( N=216 ) . Risk of anxiety symptom recurrence was significantly reduced by 81 % for quetiapine XR versus placebo : hazard ratio=0.19 ( 95 % confidence interval 0.12–0.31 ; P<0.001 ) . Fewer patients receiving quetiapine XR ( N=22 , 10.2 % ) than placebo ( N=84 , 38.9 % ) experienced anxiety symptom recurrence . Significant differences were observed between quetiapine XR and placebo in : HAM-A total , psychic/somatic , CGI-S ( all P<0.001 ) and Q-LES-Q ( P<0.05 ) scores . AEs ( > 10 % ) during open-label treatment were dry mouth , sedation , somnolence , dizziness , fatigue , and constipation . During r and omized treatment , the most common AEs for quetiapine XR were headache and nasopharyngitis  . Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR , with tolerability results consistent with the known profile of quetiapine The pituitary adenylate cyclase-activating peptide ( PACAP ) and its receptor ( PAC1 ) are involved in stress response and anxiety . Genotypes for PACAP/PAC1 were examined for effects on treatment response to venlafaxine XR in  generalized anxiety disorder .  The Asp54Gly ( rs2856966 ) variant in the PACAP gene was associated with better treatment outcome BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients BACKGROUND Existing literature on panic disorder ( PD ) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy ( CBT ) , Selective Serotonin Reuptake Inhibitor ( SSRI ) or both combined ( CBT+SSRI ) . METHOD Patients were r and omized to CBT , SSRI or CBT+SSRI which each lasted one year including three months of medication taper . Participating patients kept record of the frequency of panic attacks throughout the full year of treatment . Rate of improvement on panic frequency and the relationship between rate of improvement and baseline agoraphobia ( AG ) were examined . RESULTS A significant decline in frequency of panic attacks was observed for each treatment modality . SSRI and CBT+SSRI were associated with a significant faster rate of improvement as compared to CBT . Gains were maintained after tapering medication . For patients with moderate or severe AG , CBT+SSRI was associated with a more rapid improvement on panic frequency as compared to patients receiving either mono-treatment . LIMITATIONS Frequency of panic attacks was not assessed beyond the full year of treatment . Second , only one process variable was used . CONCLUSIONS Patients with PD respond well to each treatment as indicated by a significant decline in panic attacks .  CBT is associated with a slower rate of improvement as compared to SSRI and CBT+SSRI . Discontinuation of SSRI treatment does not result in a revival of frequency of panic attacks . Our data suggest that for patients without or with only mild AG , SSRI-only will suffice . For patients with moderate or severe AG , the combined CBT+SSRI treatment is recommended One hundred six patients diagnosed according to DSM-III as suffering from agoraphobia with panic disorder , panic disorder with limited phobic avoidance , or uncomplicated panic disorder entered an acute 8-week treatment phase . Patients who improved received an additional 6 months ' maintenance treatment . Significantly more patients treated with alprazolam than with imipramine hydrochloride or placebo remained in therapy and experienced panic attack and phobia relief during the acute treatment phase . During the maintenance phase , neither tolerance nor daily dose increase was observed . All patients who completed the maintenance phase ( 27 in the alprazolam group , 11 in the imipramine group , and 10 in the placebo group ) were panic free at the end of 8 months of study treatment . Alprazolam therapy was effective and well tolerated at a mean daily dose of 5.7 mg . Imipramine hydrochloride ( 175 mg/d ) also produced significant panic relief but was associated with poor patient acceptance OBJECTIVE Older adults with anxiety disorders are burdened by impairment in neurocognition , which may be mediated by elevated circulating cortisol levels . In a r and omized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder , we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function . METHODS We examined 60 adults aged 60 years and older , who took part in a 12-week trial of escitalopram versus placebo for generalized anxiety disorder . All subjects had pre-treatment and post-treatment assessment s that included monitoring of peak and total daily cortisol  and a comprehensive neuropsychological evaluation . RESULTS Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory but no association with executive tasks ( measures of working memory and set shifting ) . Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes : memory improvement was seen with cortisol reduction among patients receiving escitalopram but not among patients receiving placebo . CONCLUSION Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of generalized anxiety disorder predicted changes in immediate and delayed memory . This finding suggests a novel treatment strategy in late-life anxiety disorders : targeting hypothalamic-pituitary- adrenal axis dysfunction to improve memory Discontinuation effects following cessation of 12 and 24 wk of pregabalin treatment for  generalized anxiety disorder ( GAD )  were evaluated in a placebo- and lorazepam-controlled , r and omized , double-blind , multicentre trial conducted in 16 countries . The study design consisted of two 12-wk treatment periods ( periods 1 and 2 ) , each followed by a 1-wk taper and two post-discontinuation assessment s , one immediately following the taper and one 1-wk post-taper . Patients were assigned to receive an initially flexible dose of pregabalin 450 - 600 mg/d , pregabalin 150 - 300 mg/d , or lorazepam 3 - 4 mg/d for 6 wk ; responders continued fixed-dose therapy for 6 additional weeks . Patients entering period 2 continued on the same fixed dose or switched to placebo .  Discontinuation effects were evaluated with the Physician Withdrawal Checklist ( PWC ) and reported discontinuation-emergent signs and symptoms . Rebound anxiety was measured with the Hamilton Anxiety Rating Scale . GAD symptoms improved with all treatments and improvements were maintained over 12 and 24 wk . Low levels of discontinuation symptoms were evident in all treatment groups . For patients who received active treatment during both periods , mean ( 95 % confidence interval ) increases on the PWC from last visit on active treatment to the second post-discontinuation assessment were : pregabalin 450 - 600 mg/d : 2.8 ( 1.6 - 3.9 ) , pregabalin 150 - 300 mg/d : 1.7 ( 0.7 - 2.8 ) , lorazepam 3 - 4 mg/d : 2.2 ( 1.0 - 3.5 ) . Rates of rebound anxiety were also low at both 12 and 24 wk ( 0 - 6 % ) . This suggests that risk of discontinuation symptoms and rebound anxiety are low for pregabalin after 12 and 24 wk of treatment Objective : To eluci date the consequences of broadening DSM-IV criteria for generalized anxiety disorder ( GAD ) , we examined prospect ively the evolution of GAD symptoms in two groups of patients ; one group diagnosed according to DSM-IV criteria and the other , according to broader criteria . Method : Multicentre , prospect i ve and observational study conducted on outpatient psychiatric clinics . Patients were selected from October 2007 to January 2009 and diagnosed with GAD according to DSM-IV criteria ( DSM-IV group ) or broader criteria . Broader criteria were considered 1-month of excessive or non-excessive worry and only 2 of the associated symptoms listed on DSM-IV for GAD diagnosis . Socio-demographic data , medical history and functional outcome measures were collected three times during a 6-month period . Results : 3,549 patients were systematic ally recruited ; 1,815 patients in DSM-IV group ( DG ) and 1,264 in broad group ( BG ) ; 453 patients did not fulfil inclusion criteria and were excluded . Most patients ( 87.9 % in DG , 82.0 % in BG ) were currently following pharmacological therapies ( mainly benzodiazepines ) to manage their anxiety symptoms . The changes observed during the study were : 49.0 % and 58.0 % , respectively of patients without anxiety symptoms as per HAM-A scale at the 6 month visit ( p=0.261 ) and 59.7 % and 67.7 % , respectively ( p=0.103 ) of responder rates ( > 50 % reduction of baseline scoring ) . Conclusion : Broadening of GAD criteria does not seem to affect psychiatric care results in subjects with GAD , is able to identify the core symptoms of the disease according to the DSM-IV criteria and could lead to an earlier diagnosis Background This naturalistic open label follow-up study had three objectives :1 ) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment2 ) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia.3 ) To observe paroxetine 's  tolerability over a 24 month period . Methods 143 patients with panic disorder ( PD ) , with or without agoraphobia , successfully finished a short-term ( ie 12 week ) trial of paroxetine treatment . All patients then continued to receive paroxetine maintenance therapy for a total of 12 months . At the end of this period , 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase . The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored , as in the first group , for another year while medication-free . The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a r and omized manner . Results Only 21 of 143 patients ( 14 % ) relapsed during the one year medication discontinuation follow-up phase . There were no significant differences in relapse rates between the patients who received intermediate-term ( up to 12 months ) paroxetine and those who chose the long-term course ( 24 month paroxetine treatment ) . 43 patients ( 30.1 % ) reported sexual dysfunction . The patients exhibited an average weight gain of 5.06 kg . All patients who eventually relapsed demonstrated significantly greater weight increase ( 7.3 kg ) during the treatment phase . Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation . Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment CONTEXT Generalized anxiety disorder ( GAD ) is a chronic disorder in need of reliable data to guide long-term treatment . OBJECTIVES To assess the benefits of 6 and 12 months ' treatment of GAD with venlafaxine hydrochloride extended release ( XR ) in patients who improved after 6 months ' open-label venlafaxine XR treatment . DESIGN After 6 months ' open-label venlafaxine XR treatment , improved patients were r and omized to venlafaxine XR or placebo for 6 months . All venlafaxine XR patients still in the study at 12 months were r and omized to receive venlafaxine XR or placebo , and all placebo patients continued taking placebo for another 6 months . SETTING One urban site ( 5 locations ) . PATIENTS Of 268 patients with a diagnosis of GAD entering the open-label venlafaxine XR treatment phase , 158 ( 59.0 % ) completed 6 months , and 136 ( 50.7 % ) entered relapse phase 2 ( 6 - 12 months ) . Fifty-nine ( 43.4 % ) of 136 patients entered phase 3 ( 12 - 18 months ) . INTERVENTION Six months ' open-label treatment with venlafaxine XR , followed by double-blind venlafaxine XR or placebo for 2 relapse phases , each lasting 6 months . MAIN OUTCOME MEASURES Time to relapse while receiving venlafaxine XR or placebo after 6 and after 12 months of treatment . Relapse was strictly defined to safeguard against assigning patients with venlafaxine XR discontinuation symptoms or temporary anxiety increase as relapse . RESULTS For objective 1 , relapse rates in phase 2 ( months 6 - 12 ) were 9.8 % on venlafaxine XR and 53.7 % on placebo ( P < .001 ) . For objective 2 , relapse rates after 12 months on placebo ( 32.4 % ) were lower than after 6 months on venlafaxine XR ( 53.7 % ) ( P < .03 ) . CONCLUSIONS Treatment of GAD with an antidepressant should be continued for at least 12 months . Preliminary data demonstrate that improved patients who relapse while off their antianxiety medication after at least 6 months of treatment will again most likely respond to a second course of treatment with the same medication . Trial Registration clinical trials.gov Identifier : NCT00183274 Background We evaluated the effects of once-daily extended-release quetiapine fumarate ( quetiapine XR ) on patient-reported outcomes in generalized anxiety disorder ( GAD ) . Methods This is a report of a pooled analysis from three acute 8-week , r and omized , placebocontrolled , fixed-dose ( 50 , 150 , 300 mg/day ) studies and a 52-week maintenance flexible dose ( 50–300 mg/day ) study of quetiapine XR monotherapy in patients with GAD .  Quality of Life Enjoyment and Satisfaction Question naire Short Form ( Q-LES-Q-SF ) percent maximum total scores ( items 1–14 ) , item 15 ( “ satisfaction with medication ” ) , item 16 ( “ overall life satisfaction ” ) , and Pittsburgh Sleep Quality Index ( PSQI ) global scores are reported . Sheehan Disability Scale ( SDS ) total scores were also assessed ( maintenance study only ) . Results The acute studies showed significant improvements at week 8 in Q-LES-Q-SF percent maximum total score  with quetiapine XR 150 mg/day ( P < 0.001 ) and item 16  with quetiapine XR 50 ( P < 0.05 ) and 150 mg/day ( P < 0.001 ) versus placebo ; PSQI global scores significantly improved with quetiapine XR 50 , 150 , and 300 mg/day versus placebo ( P < 0.001 ) . The maintenance study showed significant benefits versus placebo with quetiapine XR 50–300 mg/day in Q-LES-Q-SF percent total score , item 15 and item 16 scores , PSQI global score , and SDS total score . Conclusion Quetiapine XR 150 mg/day ( acute studies ) and 50–300 mg/day ( maintenance study ) improved quality of life , overall functioning , and sleep quality in patients with GAD BACKGROUND This investigation assessed the effect of personality disorders ( PersDs ) on time to remission in patients with generalized anxiety disorder , social phobia , or panic disorder . METHODS Selected Axis I and II predictors of time to remission during 5 years of follow-up were assessed in 514 patients with 1 or more of these anxiety disorders who participated in the Harvard/Brown Anxiety Research Program , a multisite , prospect i ve , longitudinal , naturalistic study . RESULTS The presence of a PersD predicted a 30 % lower likelihood of generalized anxiety disorder remission , a 39 % lower likelihood of social phobia remission , and no difference in likelihood of panic disorder remission . More specifically , a lower likelihood of remission from generalized anxiety disorder was predicted by the presence of avoidant PersD ( 34 % lower ) and dependent PersD ( 14 % lower ) . The presence of avoidant PersD predicted a 41 % lower likelihood of social phobia remission . The presence of major depressive disorder did not account for these findings . CONCLUSIONS Our findings provide new data on the pernicious effect of PersDs on the course of generalized anxiety disorder and social phobia but not panic disorder , suggesting that PersDs have a differential effect on the outcome of anxiety disorders BACKGROUND Controlled prospect i ve studies of the simultaneous long-term outcome of several mental disorders are rare . This study sought to determine if there were important differences between the outcome of anxiety and depressive disorders after 12 years and to examine their main predictors . METHOD A cohort of 210 people seen in general practice psychiatric clinics with a DSM-III diagnosis of generalized anxiety disorder ( 71 ) , panic disorder ( 74 ) , or dysthymic disorder ( 65 ) , including combined anxiety-depressive disorder ( cothymia ) ( 67 ) was followed up after 12 years . Interview assessment s of symptoms , social functioning and outcome were made , the latter using a new scale , the Neurotic Disorder Outcome Scale . Seventeen baseline predictors were also examined . RESULTS Data were obtained from 201 ( 96 % ) patients , 17 of whom had died . Only 73 ( 36 % ) had no DSM diagnosis at the time of follow-up . Using univariate and stepwise multiple linear regression those with cothymia , personality disorder , recurrent episodes and greater baseline self-rated anxiety and depression ratings had a worse outcome than others ; initial diagnosis did not contribute significantly to outcome and instability of diagnosis over time was much more common than consistency . CONCLUSION Only two out of five people with the common neurotic disorders have a good outcome despite alleged advances in treatment . Those with greater mood symptoms and pre-morbid personality disorder have the least favourable outcome . It is suggested that greater attention be paid to the concurrent treatment of personality disorder and environmental factors rather than symptoms as these may be the real cause of apparent treatment resistance Carbon dioxide ( CO2 ) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder ( PD ) . Anti-panic drugs decrease CO2 reactivity after the first days of treatment ; however , the clinical meaning of this finding has not yet been established . This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors ( SSRIs ) on CO2 reactivity and compared the relationships between 35 % CO2 hyperreactivity modulation and short-term clinical outcome .  One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were r and omly assigned to treatment groups with imipramine , clomipramine , paroxetine , sertraline , or fluvoxamine . A double-blind , r and omized design was applied . Each patient received the 35 % CO2 challenge on days 0 , 7 , and 30 . The severity of clinical symptomatology was measured on days 0 and 30 . Decreased hyperreactivity to 35 % CO2 in all five treatment groups was already evident after the first week . The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement . Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month . The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity . They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “ respiratory ” PD BACKGROUND Generalized anxiety disorder  ( GAD ) is a common and serious disease with a lifetime prevalence of 4.3 % to 5.9 % . It is underdiagnosed in primary care . METHODS Recommendations on the treatment of GAD are given on the basis of all available findings from pertinent r and omized trials , retrieved by a selective search of the literature . RESULTS Among psychotherapeutic techniques , various kinds of cognitive behavioral therapy ( CBT ) have been found useful in controlled trials . The drugs of first choice include selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-norepinephine reuptake inhibitors ( SNRIs ) , and the calcium-channel modulator pregabalin . Tricyclic antidepressants are also effective but have more adverse effects than SSRIs . Although benzodiazepines are effective anxiolytic agents for short-term use , they should not be given over the long term because of the danger of addiction . Buspirone , an azapirone , was found to be effective in a small number of trials , but the findings across trials are inconsistent . The response rate of GAD to CBT in published studies lies between 47 % and 75 % , while its response rate to drug treatment lies between 44 % and 81 % . CONCLUSION The treatment of GAD with CBT and drugs is evidence -based and has a good chance of improving the manifestations of the disorder OBJECTIVE This study evaluated the efficacy and tolerability of agomelatine in the prevention of relapse in patients with generalized anxiety disorder ( GAD ) . METHOD Patients with GAD ( Hamilton Anxiety Rating Scale [ HARS ] ≥ 22 , with items 1 and 2 ≥ 2 , item 1 + 2 ≥ 5 ; Montgomery-Asberg Depression Rating Scale [ MADRS ] ≤ 16 ; and < 20 % decrease in HARS total score between screening and baseline ) who responded to a 16-week course of agomelatine 25 - 50 mg/d treatment were r and omly assigned to receive continuation treatment with agomelatine ( n = 113 ) or placebo ( n = 114 ) for 26 weeks . The main outcome measure was time to relapse during this maintenance period . The estimated risk of relapse was calculated using the Kaplan-Meier method , and groups were compared using a log-rank test stratified for country . The study was undertaken in 31 clinical centers in Canada , Denmark , Estonia , Finl and , Hungary , and Sweden from November 2007 to September 2009 . RESULTS During the 6-month maintenance period , the proportion of patients that relapsed during the double-blind period in the agomelatine group ( 22 patients , 19.5 % ) was lower than in the placebo group ( 35 patients , 30.7 % ) . The risk of relapse over time was significantly lower for patients who continued treatment than for those switched to placebo ( P = .046 , log-rank test stratified for country ) . Agomelatine was also superior to placebo in preventing relapse in the subset of more severe patients with baseline HARS total score ≥ 25 and CGI-S score ≥ 5 . The tolerability  of agomelatine was good throughout the study , and there were no differences in discontinuation symptoms after withdrawal of agomelatine in comparison to maintenance on agomelatine . CONCLUSIONS The present study extends the positive findings of an earlier short-term study of agomelatine in GAD , demonstrating that agomelatine is effective and well-tolerated in the longer-term treatment of this chronic disorder . TRIAL REGISTRATION www.is rct n.org identifier : IS RCT N38094599 OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines , out patients ( N = 106 ) with a lifetime diagnosis of generalized anxiety disorder ( current diagnosis could be subthreshold ) who had been treated with a benzodiazepine for 8–52 weeks were stabilized for 2–4 weeks on alprazolam in the range of 1–4 mg/day . Patients were then r and omized to 12 weeks of double-blind treatment with either pregabalin 300–600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25 % per week , followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment . Outcome measures included ability to remain benzodiazepine-free ( primary ) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist ( PWC ) . At endpoint , a non-significant higher proportion of patients remained benzodiazepine-free  receiving pregabalin compared with placebo ( 51.4 % vs 37.0 % ) . Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score  versus placebo ( −2.5 vs + 1.3 ; p < 0.001 ) , and lower endpoint mean PWC scores ( 6.5 vs 10.3 ; p = 0.012 ) . Thirty patients ( 53 % ) in  the pregabalin group and 19 patients ( 37 % ) in the  placebo group completed the study , reducing the power to detect a significant difference on the primary outcome . The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy A multicenter , r and omized , placebo-controlled , double-blind study was conducted to evaluate the efficacy of pregabalin in preventing relapse of generalized anxiety disorder ( GAD )  after response to short-term treatment . Out patients ( n=624 ) with GAD for ≥1 year received open-label pregabalin ( 450 mg/day ) for 8 weeks and , if a clinical response was observed , were r and omized to receive either pregabalin ( 450 mg/day ; n=168 ) or placebo ( n=170 ) for 24 weeks . The primary efficacy parameter was time to relapse . Among responders to open-label acute treatment with pregabalin  , time to relapse of GAD was significantly longer for patients treated with pregabalin compared with placebo ( P<0.0001 ) . Fifty per cent of the placebo group had relapsed by day 23 , and at study endpoint , 65 % had relapsed . In the pregabalin group , only 42 % had relapsed by study end . Total attrition during double-blind treatment was somewhat higher on pregabalin compared with placebo ( 21.4 vs. 15.3 % ) ; attrition owing to adverse events ( AEs ) was also somewhat higher on pregabalin ( 6.0 vs. 2.4 % ) . AEs were relatively low in the double-blind phase ; only three AEs occurred with an incidence of more than 5 % on pregabalin and placebo , respectively : infection ( 14.9 vs. 11.2 % ) , headache ( 10.1 vs. 11.2 % ) , and somnolence ( 6.0 vs. 0 % ) . No safety concerns were identified with long-term treatment . The study indicates that pregabalin is an effective treatment for the prevention of relapse in patients with GAD OBJECTIVE This study aims to evaluate the differential predictive values of age , age of onset and duration of illness on  paroxetine  and cognitive-behavioural therapy ( CBT ) outcome in late-life panic disorder with agoraphobia . METHOD Patients 60 years and older with a confirmed diagnosis of panic disorder with agoraphobia ( n = 49 ) were r and omly assigned to paroxetine ( 40 mg/day ) treatment , individual CBT or a waiting-list control condition . Multiple regression analyses were conducted per treatment arm with post-treatment avoidance behaviour and agoraphobic cognitions as the dependent variables . RESULTS Higher age at onset and shorter duration of illness were predictors of superior outcomes following CBT , although these variables did not influence the treatment effects of paroxetine . CONCLUSIONS In late-life agoraphobic panic disorder , chronological age has no impact on treatment modality outcome . In older patients with a late disease onset or shorter duration of illness , CBT is to be preferred over paroxetine , whereas paroxetine might be the treatment of choice for older people with an early onset and short duration of illness It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse . This study further explores the relationship between relapse and duration of imipramine treatment in this population . Fifty-one patients , all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and r and omized to double-blind maintenance or placebo substitution , discontinued imipramine treatment eventually and were followed over a 12-month risk period : 27 during first year placebo substitution , 7 after 12 months of imipramine maintenance in placebo substitution , and 17 after variable duration s of imipramine maintenance in open discontinuation . There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation . Duration of imipramine treatment , the method of discontinuation ( open versus placebo substitution ) , or any of the 9 variables from the demographic , clinical , and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse . The rate of relapse after only 6 months of treatment ( 10 out of 27 , 37 % ) was identical to the rate of relapse after 12 to 30 months of treatment ( 9 out of 24 , 37.5 % ) . The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients . Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction BACKGROUND Panic disorder ( PD ) is generally regarded as a chronic condition with considerable variation in severity of symptoms . AIMS To describe the long-term outcome of naturalistically treated PD . METHODS Fifty-five out patients with PD , who participated in a placebo-controlled drug trial of the efficacy of alprazolam and imipramine 15 years ago were reassessed with the same instruments used in the original study . RESULTS Complete recovery ( no panic attacks and no longer on medication during the last 10 years ) was seen in 18 % of patients , and an additional 13 % recovered but were still on medication . Fifty-one percent experienced recurrent anxiety attacks whereas 18 % still met diagnostic criteria for PD . The incidence of agoraphobia decreased from 69 % to 20 % . Patients with agoraphobia at admission tended to have a poorer long-term outcome according to daily functioning compared with patients without agoraphobia at admission , although both groups reported improved daily functioning at follow-up . Maintenance medication was common . No benzodiazepine abuse was reported . CONCLUSION PD has a favourable outcome in a substantial proportion of patients . However , the illness is chronic and needs treatment . The short-term treatment given in the drug trial had no influence on the long-term outcome Objective : Generalized anxiety disorder ( GAD ) is common in older adults and can be treated with selective serotonin reuptake inhibitors ( SSRIs ) . Genetic variation in the serotonin transporter gene promoter region is posited to be associated with SSRI efficacy : 2 polymorphisms ( 5-HTTLPR S/L and rs25531 g/a ) form a haplotype with the La combination having higher transcription activity than other haplotypes . We hypothesized that GAD patients with no La haplotypes ( La− ) have lower SSRI treatment efficacy than those with 1 to 2 La haplotypes ( La+ ) . Method : The study enrolled subjects aged 60 years or older with a principal diagnosis of GAD into a 12-week , r and omized trial of escitalopram versus placebo . One hundred fifty subjects were genotyped for the serotonin transporter promoter region haplotype and were divided into La− and La+ genotype groups ; the primary analyses were done in European Americans only ( n = 125 ; n = 59 with escitalopram and n = 66 with placebo ) . Results : Escitalopram  had no efficacy in the La− group versus moderate efficacy in the La+ group . This genetic moderation of SSRI efficacy was due to a higher placebo response in La− subjects , compared with La+ subjects . Drug concentration did not affect the genetic results . Exploratory analyses suggest that La− subjects had greater variability of anxiety symptoms unrelated to treatment . Conclusions : The serotonin transporter promoter haplotype is associated with variability in SSRI efficacy for late-life GAD . The variability may result from a genetic effect on anxiety symptom variability unrelated to treatment , rather than a pharmacodynamic effect that has been previously assumed . Further research is needed to underst and the pharmacogenetic mechanism of this haplotype Antidepressant drugs are the preferred choice for the treatment of generalized anxiety disorder ( GAD ) . However , the choice of pharmacotherapy is determined on a trial- and -error basis , as the underlying mechanisms of treatment response are unknown . We examined whether the COMT gene , which has been known to play a role in antidepressant treatment response in major depressive disorder ( MDD ) , has a pharmacogenetic effect in antidepressant treatment response in GAD . In our study , 156 patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study . Genotypes were obtained for the COMT functional variant rs4680 ( Val158Met ) for all patients ; however , pharmacogenetic analysis was only conducted for the European American population ( n=112 ) . We found no significant association between our primary Hamilton Anxiety Scale outcome measure and rs4680 . However , we did find a nominally significant allelic association between this variant and a secondary treatment outcome measure ( CGI-I ) in our European American population ( n=112 ) . Furthermore , we show a slight dominant effect of the A-allele with the CGI-I measure in the European American population indicating a possible pharmacogenetic role of rs4680 in antidepressant treatment outcome in GAD . Further studies in a larger population are needed to confirm this effect Hendriks G‐J , Keijsers GPJ , Kampman M , Oude Voshaar RC , Verbraak MJPM , Broekman TG , Hoogduin CAL . A r and omized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder Abstract Objective : Short-term clinical trials have demonstrated the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder ( GAD ) . This study examined long-term safety and tolerability of pregabalin in patients with GAD , social anxiety disorder ( SAD ) , or panic disorder ( PD ) . Research design and methods : Patients ( n = 528 ) completing one of four r and omized , double-blind , placebo-controlled trials of pregabalin for GAD , SAD , or PD were treated , open label , with flexible-dose pregabalin ( 150–600 mg/day ) for 1 year . Clinical trial registration : NCT00150449 . Main outcome measures : The primary outcomes were safety and tolerability . Illness severity was assessed at baseline and Weeks 27/52 using the Clinical Global Impression of Severity ( CGI-S ) scale . Patients were characterized as ‘ responders ’ or ‘ non-responders ’ based on CGI-S scores ≤2 and > 2 , respectively . Analyses were performed on the total anxiety ( GAD , SAD and PD ) and GAD groups . Results : During 1 year of treatment with pregabalin  , dizziness ( 12.5 % ) was the only treatment-related adverse event ( AE ) occurring ≥10 % . Somnolence , weight gain , headache and insomnia occurred at 7.6 % , 5.5 % , 5.3 % and 4.7 % , respectively . Few treatment-related AEs were rated as severe in the total anxiety ( 5.1 % ) or GAD ( 3.6 % ) groups . Discontinuation rates due to AEs were similar ( 9.7 % and 10.6 % , respectively ) . No clinical ly significant laboratory , electrocardiogram , or other treatment-related safety findings were noted , except for treatment-related weight gain , which occurred in both the total ( 24.4 % ) and GAD ( 19.4 % ) groups . Mean CGI-S scores were similar at baseline in the total ( n = 528 ; score , 3.4 ) and GAD groups ( n = 330 ; score , 3.6 ) , and CGI-S responder rates were similar at last-observation-carried-forward endpoint ( 51.3 % and 48.1 % , respectively ) . Conclusions : Pregabalin was generally well tolerated in the long-term treatment of anxiety disorders . Improvement in illness severity was maintained over time . The key limitations of this study were that it was not r and omized and neither placebo- nor active-comparator-controlled Objectives : Selective serotonin reuptake inhibitors ( SSRIs ) are currently considered as the first drug of choice in the treatment of panic disorder ( PD ) . The aim of this long-term , naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD . Outcome measures included relapse rates and adverse effects . Methods : Two hundred patients with PD were enrolled in our study . All subjects met DSM-IV criteria for PD or PD with agoraphobia ( PDA ) . All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram ( n = 50 ) , fluoxetine ( n = 50 ) , fluvoxamine ( n = 50 ) , or paroxetine ( n = 50 ) in a r and omized , nonblinded fashion . Both the treating psychiatrist and the patients were not blind to the assigned treatment , but the clinician raters were blind to the study medication . The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists . The Panic Self- Question naire , which is a self-report scale , was administered at baseline and then once per month during the duration of the 12-month study . The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study . Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits . The body weight of study subjects was measured at baseline , and then at the 12th month visit end point . Results : Of 200 patients who entered the study , 127 patients ( 63.5 % ) completed the full 12-month protocol . Retention rates were highest for paroxetine ( 76 % [ 38/50 ] ) , intermediate for citalopram ( 68 % [ 34/50 ] ) and fluvoxamine ( 60 % [ 30/50 ] ) , and lowest for fluoxetine ( 50 % [ 25/50 ] ) . Patients who completed the 12-month protocol responded favorably to the study treatment . The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8 . At visits on months 3 , 6 , 9 , and 12 , however , there were no statistically significant differences between the 4 groups in relapse rates ( defined as the occurrence of 1 or more panic attacks during the previous week of treatment ) ( F1,127 = 0.17 ; P = 0.13 [ not statistically significant ] ) . At the 12th month end point , patients in all 4 treatment groups had a statistically significant increase in body weight . Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment . Reports of sexual adverse effects at the 12th month visit were similar in the citalopram , fluoxetine , and paroxetine groups , but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit . Conclusions : Most of our PD patients responded well to 12-month treatment with either citalopram , fluoxetine , fluvoxamine , or paroxetine , and the overall response rate was equal after the first 4 weeks of treatment . Although patients treated with paroxetine had the lowest dropout rates during the initiation phase , they had the highest rate of adverse effects as measured at the 12th month visit . Conversely , patients in the fluvoxamine group had the highest dropout rate ( which was primarily caused by adverse effects in the initiation phase of treatment . ) ; however , patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents . Overall , when measured at the 12th month visit , monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine . In addition , monotherapy with paroxetine , citalopram , and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine BACKGROUND This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD . METHODS Analysis of patient-reported data from a r and omized-withdrawal , double-blind , placebo-controlled study of quetiapine XR monotherapy in GAD . Following open-label run-in ( 4 - 8 weeks ) and a 12 - 18-week stabilization phase ( quetiapine XR 50 , 150 , or 300 mg/day ) , eligible patients were r and omized to continue on quetiapine XR or receive placebo for up to 52 weeks . Primary variable was time to an anxiety event . Secondary variables included the Sheehan Disability Scale ( SDS ) and Pittsburgh Sleep Quality Index ( PSQI ) . RESULTS In total , 432 patients were r and omized ( quetiapine XR , N=216 ; placebo , N=216 ) . The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo ( HR 0.19 ; 95 % CI 0.12 , 0.31 ; p<0.001 ) . Quetiapine XR was more effective than placebo at maintaining SDS total scores ( LSM change : -0.19 vs. 1.01 ; p=0.017 ) and non-work-related SDS domain score ' family life/home responsibilities ' ( -0.13 vs. 0.32 ; p=0.011 ) , but not ' social life ' ( 0.05 vs. 0.34 ; p=0.114 ) . Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ' days lost ' ( -0.05 vs. 0.11 ; p=0.027 ) , but not ' work/school ' ( -0.10 vs. 0.29 ; p=0.051 ) or ' days underproductive ' ( 0.06 vs. 0.13 ; p=0.619 ) . PSQI global scores were reduced from r and omization with quetiapine XR vs. placebo ( 0.39 vs. 1.60 ; p<0.001 ) . LIMITATIONS Lack of active-comparator arm , exclusion of patients with comorbid depression . CONCLUSIONS In patients with GAD , long-term treatment with quetiapine XR ( 50 - 300 mg/day ) monotherapy was effective at maintaining improvements in functioning and sleep quality BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs OBJECTIVE Generalized anxiety disorder is common among older adults and leads to diminished health and cognitive functioning . Although antidepressant medications are efficacious , many elderly individuals require augmentation treatment . Furthermore , little is known about maintenance strategies for older people . The authors examined whether sequenced treatment combining pharmacotherapy and cognitive-behavioral therapy ( CBT ) boosts response and prevents relapse in older adults with generalized anxiety disorder . METHOD Participants were individuals at least 60 years of age with generalized anxiety disorder ( N=73 ) who were recruited from outpatient clinics at three sites . Participants received 12 weeks of open-label escitalopram and were then r and omly assigned to one of four conditions : 16 weeks of escitalopram ( 10 - 20 mg/day ) plus modular CBT , followed by 28 weeks of maintenance escitalopram ; escitalopram alone , followed by maintenance escitalopram ; escitalopram plus CBT , followed by pill placebo ; and escitalopram alone , followed by placebo . RESULTS Escitalopram augmented with CBT  increased response rates on the Penn State Worry Question naire but not on the Hamilton Anxiety Rating Scale compared with escitalopram alone . Both escitalopram and CBT prevented relapse compared with placebo . CONCLUSIONS This study demonstrates effective strategies for treatment of generalized anxiety disorder in older adults . The sequence of antidepressant medication augmented with CBT leads to worry reduction in the short-term . Continued medication prevents relapse , but for many individuals , CBT would allow sustained remission without requiring long-term pharmacotherapy High-potency benzodiazepines , such as clonazepam , are frequently used in the treatment of panic disorder ( PD ) because of their rapid onset of action and good tolerability . However , there is concern about their potential to cause withdrawal symptoms . We aim ed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years . A specific scale for judging withdrawal was also developed , the Composite Benzodiazepine Discontinuation Symptom Scale . We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication . The trial consisted of a 4-month period of tapering and an 8-month follow-up period . The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached , followed by a decrease of 0.25 mg per week . The mean dosage at the start of tapering was 2.7 ± 1.2 mg/d . In total , 51 ( 68.9 % ) of the patients were free of the medication after the 4 months of tapering according to the protocol , and 19 ( 26.0 % ) of the patients needed another 3 months to be free of  medication . Clonazepam discontinuation symptoms were mostly mild and included mainly : anxiety , shaking/trembling/tremor , nausea/vomiting , insomnia/nightmares , excessive sweating , tachycardia/palpitations , headache , weakness , and muscle aches . The improvement in PD and general well-being was maintained during both the taper and follow-up phases . Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually . We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk
target: Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy .
  Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD .
  Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine .
  We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .
background: Many aspects of long-term pharmacological treatments for  anxiety disorders ( AnxDs ) are still debated .
  We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .