title: EHMTI-0031. Efficacy and safety of venlafaxine for the treatment of chronic migraine: a randomized, double-blind, controlled trial A comparative study of amitriptyline and fluvoxamine in migraine prophylaxis. Fluoxetine for migraine prophylaxis: a double-blind trial. Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study Amitriptyline Versus Amitriptyline Combined With Fluoxetine in the Preventative Treatment of Transformed Migraine: A Double‐Blind Study The efficacy and safety of venlafaxine in the prophylaxis of migraine. Double‐Blind Trial of Fluoxetine: Chronic Daily Headache and Migraine Fluoxetine prophylaxis of migraine. Femoxetine in the prophylaxis of migraine ‐ A randomised comparison with placebo Escitalopram and Venlafaxine for the Prophylaxis of Migraine Headache Without Mood Disorders Paroxetine in the Treatment of Chronic Daily Headache Selective serotonin reuptake inhibitors for migraine prophylaxis. Canadian Headache Society guideline for migraine prophylaxis. A randomized general practice * group‐comparative study of femoxetine and placebo in the prophylaxis of migraine S-Fluoxetine in the Prophylaxis of Migraine: A Phase II Double-Blind Randomized Placebo-Controlled Study Migraine and reduced work performance Propranolol and femoxetine, a HT-uptake inhibitor, in migraine prophylaxis. A double-blind crossover study. Evaluation of the Prophylactic Efficacy of Amitriptyline and Citalopram, Alone or in Combination, in Patients with Comorbidity of Depression, Migraine, and Tension-Type Headache
abstract: Conclusions In this double-blind , r and omized study extended-release venlafaxine 150 mg/day found to be effective in chronic migraine . Our study showed a clear effect that was in subgroup of subjects with medication overuse . In addition , in this study , the low number of adverse events showed venlafaxine to be well tolerated . Future controlled trials expended lon ger with larger sample size , should also support the effectiveness and safety of venlafaxine in patients suffering from chronic migraine . No conflict of interest Current treatment of migraine either abortive or prophylactic is often unsatisfactory . Prophylactic treatment of severe migraine  may reduce attack frequency , and current therapy centers on beta-blockers , serotonin ( 5-HT ) reuptake blockers and 5-HT2 receptor antagonists . The author compared the efficacy and safety of amitriptyline and fluvoxamine among migraine patients ( 24F , 8 M vs. 23F , 9 M ) in a double blind study . The efficacy of amitriptyline has already been established by earlier clinical studies . The other investigated drug , fluvoxamine , has a more selective 5-HT reuptake blocking property than amitriptyline . In this study , amitriptyline significantly reduced the number of headache attacks , but it caused severe drowsiness in many migraineurs . The fluvoxamine also favorably influenced on the number of headache attacks and caused only slight side effects . These findings suggest , that fluvoxamine may be an alternative drug in migraine prophylaxis , however , further studies should be performed with more subjects UNLABELLED Selective serotonin reuptake inhibitors have recently been used in the treatment of migraine . OBJECTIVE We studied the safety and efficacy of fluoxetine in the prevention of migraine . PATIENTS Between February 1997 and December 1997 , we examined 52 patients ( 33 women ) at the Headache Diagnosis and Therapy Service of the Second University of Naples . Ages ranged from 18 to 65 years , and all patients suffered from migraine without aura according to IHS 1988 criteria . The sample was divided into two groups : group A included 32 patients ( 19 women ; mean age , 36.8 years [ SD 12.4 ] ) who received fluoxetine at a dosage of 20 mg per day ; group B included 20 patients ( 14 women ; mean age , 38.8 years [ SD 15.6 ] ) who received placebo . METHODS Our study was a single-center , r and omized , double-blind , parallel study of fluoxetine for the prophylactic control of migraine and consisted of two phases : 30 days of pharmacological wash out and 6 months of therapy with monthly follow-up . Patients were r and omly assigned to two groups : A , fluoxetine or B , placebo . At the first visit , patients provided a detailed history and underwent neurological evaluation and a Zung test for depression . No pathological values were revealed . In order to monitor symptomatology , all patients received a form for the calculation of the total pain index at monthly follow-up . RESULTS A comparison of the total pain index between basal values ( calculated during the period of wash out ) and monthly follow-up ( calculated monthly during the period of 6 months of the therapy ) showed significant reduction ( P < .05 ) beginning from the third month of treatment in the fluoxetine group and no significant reduction in the placebo group . CONCLUSION Even if preliminary and to be confirmed , these data seem to support the use of fluoxetine in the treatment of migraine In patients with migraine with or without aura the prophylactic effect of amitriptyline ( AMT ) and venlafaxine ( VLF ) was compared in a r and omized double-blind crossover study . Intolerable side effects result ed in drop out of five patients on AMT  ( due to hypersomnia , difficulty in concentration and orthostatic hypotension ) and one patient on VLF ( because of nausea and vomiting ) . Following the run-in period the patients ( n = 52 ) were r and omly treated with one of the study medications for 12 weeks . After a wash-out period lasting 4 weeks the patients were treated with the other drug for further 12 weeks . Both drugs had significant beneficial effect on pain parameters . Total number of side effects of VLF was low when compared with the side effect profile of AMT . In conclusion , it is suggested that VLF may be considered for the prophylaxis of migraine because of its low and /or tolerable side effect properties Background and Objectives .—Antidepressants are often used to treat chronic daily headache disorders such as transformed migraine , in part because of the high prevalence of associated mood disorder . We conducted this study to evaluate the efficacy and tolerability of combined treatment with amitriptyline and fluoxetine compared with amitriptyline alone for chronic daily headache due to transformed migraine OBJECTIVE To evaluate the efficacy and safety of venlafaxine in the prophylaxis of migraine . BACKGROUND The efficacy of venlafaxine , which is selectively effective on the serotonergic and noradrenergic mechanisms , on various headaches and chronic pain syndromes has been demonstrated . To our knowledge , this is the first placebo-controlled , double-blind , r and omized study of two different doses of venlafaxine for migraine treatment . METHODS In this prospect i ve study , 60 migraine patients without aura were r and omly assigned to venlafaxine XR 75 mg , venlafaxine XR 150 mg , or placebo . The frequency of headache attacks , the severity and the duration of attacks , and analgesic use were monitored every 2 weeks for 2 months . Adverse events and patient satisfaction were also evaluated during these visits . At the end of the 2 months , global efficacy and tolerance were investigated . RESULTS A significant difference was observed between the venlafaxine 150 mg and placebo groups in the number of headache attacks ( P= .006 ) . According to patient satisfaction comparisons , the active drug groups were significantly different when compared with placebo ( P= .001 at visit 2 and visit 6 ) . When the global efficacy was considered , 80 % of patients in the 75-mg group and 88.2 % of the patients in the 150-mg group evaluated treatment benefits as either good or very good . CONCLUSIONS Venlafaxine was more effective than placebo and is safe and well tolerated as migraine prophylaxis SYNOPSIS Many patients with severe migraine remain refractory to the current treatment regimens or can not tolerate the side effects . Since current research implicates serotonin dysregulation in migraine pathogenesis , we investigated in a double blind , placebo controlled study the prophylactic effect of the serotonergic drug fluoxetine .  Sixteen subjects were r and omly assigned to 8 week fluoxetine treatment and 16 to the placebo group ; nine subjects in each group completed the study .  Migraine headache scores were obtained for two weeks prior to commencement of treatment , and then for each successive two week period . Zung depression scores were obtained before and after completion of the study . Fluoxetine caused significant reduction in headache scores starting with weeks 3 - 4 of treatment ; there was no significant change with placebo .  Depression scores did not differ between groups before treatment , and did not significantly change with either treatment . Fluoxetine appears to be a safe and effective drug for migraine prophylaxis , and deserves further therapeutic trials with larger groups for longer periods of time The prophylactic effect in migraine of femoxetine , a 5‐HT‐uptake inhibitor , was compared to that of placebo in a double‐blind group‐comparative study . A total of 59 patients , referred to the department from general practitioners , was stratified according to age , sex , duration , and frequency of attacks and then allocated at r and om to treatment with either femoxetine or placebo . Each patient was treated for 12 weeks with 200 mg in the first week and 300 in the remaining weeks . Ten patients on femoxetine and four patients on placebo failed to complete the study There is evidence that some antidepressant drugs are beneficial in the prophylaxis of  migraine .  Previous reports have shown that migraine patients may respond to various antidepressant agents used for prophylactic therapy . The main purpose of this study was to compare the efficacy of antidepressants from 2 different groups ( venlafaxine vs escitalopram ) on people who had migraine headache without depression or anxiety . In this prospect i ve study , we evaluated the headache diaries of 93 patients who were being treated with venlafaxine ( n = 35 ) and escitalopram ( n = 58 ) . At the end of the 3-month period , patients were reassessed , and those with marked differences in attack frequency , duration , intensity ( with visual analog scales ) , lost work-day equivalent index , and migraine disability assessment question naire were compared . There was a clear reduction in headache frequency ( P < 0.0001 ) , duration ( P < 0.0001 ) , and severity ( P < 0.0001 ) in the venlafaxine group . In addition , there was a significant improvement in daily work performance during headaches ( P < 0.0001 ) . In the escitalopram group , monthly headache frequency ( P < 0.026 ) , duration ( P < 0.002 ) , and intensity ( P < 0.027 ) all decreased significantly , although not to the same extent as with venlafaxine . After the third month of venlafaxine and escitalopram treatment , most of the patients ( 82.8 % vs 96.5 % ) were seen to have moved to the minimal or infrequent migraine disability assessment group . According to our findings , venlafaxine and escitalopram are both effective in the prophylaxis of migraine headache without depression and anxiety . This effect was independent of mood disorder . Escitalopram should be the first choice because of its fewer side effects , but venlafaxine may be used if escitalopram is found to be insufficient SYNOPSIS The objective of this study was to assess the efficacy of sertraline in migraine prophylaxis . Other selective serotonin reuptake inhibitors have been studied for migraine prophylaxis , but this is the first report with sertraline .  Twenty-seven subjects were enrolled and baseline assessment of migraine frequency and severity were measured over a 4-week period . Subjects were then r and omized to receive placebo or sertraline in a double-blind fashion with headache frequency and severity measured over an 8-week period . Subjects completed a daily diary reporting the occurrence , severity , and degree of impairment associated with migraine . The headache index , a composite measure of migraine frequency and severity , scores did not significantly improve between assessment s at baseline ( 20.8 + /- 14.88 ) , 8 weeks ( 17.6 + /- 12.27 ) , and 12 weeks ( 16.7 + /- 6.38 ) in the treatment group ( n=6 ) ( P=0.956 ) . This finding is compared to other studies with the serotonin selective reuptake inhibitors , fluoxetine , fluvoxamine , and paroxetine . The authors believe that the selective serotonin reuptake inhibitors are not as effective as conventional migraine prophylaxis medications such as beta-blockers , tricyclic antidepressants , or divalproex sodium , but that in patients with comorbid depression who have failed conventional therapy selective serotonin reuptake inhibitors may be effective OBJECTIVES The primary objective of this guideline is to assist the practitioner in choosing an appropriate prophylactic medication for an individual with migraine , based on current evidence in the medical literature and expert consensus . This guideline is focused on patients with episodic migraine ( headache on ≤ 14 days a month ) . METHODS Through a comprehensive search strategy , r and omized , double blind , controlled trials of drug treatments for migraine prophylaxis and relevant Cochrane review s were identified . Studies were grade d according to criteria developed by the US Preventive Services Task Force . Recommendations were grade d according to the principles of the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group . In addition , a general literature review and expert consensus were used for aspects of prophylactic therapy for which r and omized controlled trials are not available . RESULTS Prophylactic drug choice should be based on evidence for efficacy , side-effect profile , migraine clinical features , and co-existing disorders . Based on our review , 11 prophylactic drugs received a strong recommendation for use ( topiramate , propranolol , nadolol , metoprolol , amitriptyline , gabapentin , c and esartan , butterbur , riboflavin , coenzyme Q10 , and magnesium citrate ) and 6 received a weak recommendation ( divalproex sodium , flunarizine , pizotifen , venlafaxine , verapamil , and lisinopril ) . Quality of evidence for different medications varied from high to low . Prophylactic treatment strategies were developed to assist the practitioner in selecting a prophylactic drug for specific clinical situations . These strategies included : first time strategies for patients who have not had prophylaxis before ( a beta-blocker and a tricyclic strategy ) , low side effect strategies ( including both drug and herbal/vitamin/mineral strategies ) , a strategy for patients with high body mass index , strategies for patients with co-existent hypertension or with co-existent depression and /or anxiety , and additional monotherapy drug strategies for patients who have failed previous prophylactic trials . Further strategies included a refractory migraine strategy and strategies for prophylaxis during pregnancy and lactation . CONCLUSIONS There is good evidence from r and omized controlled trials for use of a number of different prophylactic medications in patients with migraine . Medication choice for an individual patient requires careful consideration of patient clinical features ABSTRACT — In a r and omized general practice study , the prophylactice effect of femoxetive ( a 5HT uptake inhibitor ) was compared with placebo in migraine patients . Treatment , with separate r and omization schedules in each practice , was allocated to 65 patients . Each patient was treated for 16 weeks with 200 mg increasing during the first nine days to 600 mg daily . No effect of femoxetine could be demonstrated in attack frequency and headache index . Separate analysis of maximum reduction in serotonin concentration during treatment revealed no difference in efficacy when compared with placebo . This supports earlier studies that femoxetine generally exerts no prophylactic effect on migraine , and the hypothesis that platelet 5HT might be of major importance in the pathogenesis of migraine is not supported S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor .  Sixty-five patients needing migraine prophylaxis were recruited into a phase II , double-blind , placebo-controlled trial . After a 1-month placebo run-in , 53 patients met entry criteria with regard to attack frequency and were r and omized , 27 to S-fluoxetine and 26 to matching placebo .  Three failed to start treatment and mere were 17 early discontinuations , 9 from S-fluoxetine , 8 from placebo , at similar times and for similar reasons . The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups . This was earlier and greater ( 1.7 attacks/28 days , or 52 % ) on active therapy than on placebo ( 1.1 attacks/28 days , or 27 % ) , and statistically significant in month 2 ( F=4.93 ; p=0.033 ) and month 4 ( F=4.55 ; p=0.041 ) . As secondary measures of efficacy , migraine-days per month and Patient 's Global Impression of Disease Severity coherently reflected the changes in attack frequency . Mean attack severity and acute medication use ( doses per attack ) were unaltered by either treatment . There were no serious adverse events . Withdrawals for adverse events were four from each group but none was considered causally related . The finding of greater efficacy of S-fluoxetine than of placebo should be interpreted conservatively , since the analysis in the final month was made on only half of the entered patients . It supports progression to phase III evaluation , which was the purpose of the study objectiue This article estimates lost work days and lost work day equivalents in a population sample of migraineurs , differentiating work loss due to headache episodes that met criteria for migraine from migrainous headaches not meeting full criteria and nonmigrainous headaches . Methods A r and  om digit dialing survey of 5,071 adults identified 800 subjects with migraine headaches . By clinical examination , a sub sample of 225 met migraine diagnostic criteria ; 174 of these patients completed at least 11 weeks of daily diaries . This report concerns the subgroup of 122 individuals with regular paid employment . Subjects completed a daily diary over a 3-month period to assess the occurrence of headaches and International Headache Society ( IHS ) criteria for each headache occurrence . We report estimates of lost work days and lost work day equivalents by type of headache . Results Participants reported headaches on 8.1 work days , of which 2.2 headache days met criteria for migraine ( IHS 1.1 , 1.2 ) , and an additional 2.1 headache days were migrainous without meeting full migraine criteria ( IHS 1.7 ) . On average , migraineurs missed 1.1 days of work due to headache in 3 months , of which 0.7 lost work days were due to migraine and 0.3 were due to migrainous headaches . When at work with headache , work effectiveness was reduced 41 % for migraine headaches , 28 % for migrainous headaches , and 24 % for other headaches . Over 3 months , migraineurs experienced an average of 3.0 lost work day equivalents , of which 1.4 were due to migraine and an additional 0.7 were due to migrainous headaches . The most disabled 20 % of the participants accounted for 77 % of the lost work days ; 40 % of subjects accounted for 75 % of the lost work day equivalents . Conclusions Employed migraine sufferers experienced considerable work loss and reduced work performance due to headache . The most severely affected migraineurs accounted for most of the reduced work performance . Targeting the most severely affected persons may be necessary to reduce work loss among migraineurs substantially . NEUROLOGY The prophylactic effect of the 5-HT uptake inhibitor femoxetine was compared with propranolol ( Frekven R ) in a double-blind crossover trial of 6 months duration . Forty-nine patients commenced the trial . Twelve patients withdrew because of drug failure or failure to attend checkups ( 6 ) , side effects ( 4 ) or other non-drug related causes ( 2 ) . In the 37 patients who completed the trial there was no significant difference between propranolol 160 mg and femoxetine 400 mg with respect to the number of headache days or the number of migraine attacks during the last 2 months of each treatment , Propranolol , however , was superior to femoxetine when the headache index was used ( P less than 0.05 ) . The study has shown that partial depletion of thrombocyte 5-HT by a 5-HT uptake inhibitor does not lead to a marked improvement in all patients contrary to what might be expected from the 5-HT hypothesis of migraine . Nevertheless , due to the infrequent subjective side effects associated with femoxetine treatment it may be a valuable prophylactic drug to a subgroup of migraine patients Antidepressants are used to treat chronic daily headache disorders such as  migraine  and chronic tension-type headache ( TTH ) , which are often associated with depression and anxiety . Here , we studied the efficacy and tolerability of amitriptyline and citalopram , given alone or in combination , in patients with ‘ triple ’ comorbidity of depression , TTH , and migraine . Eighty-eight patients were enrolled in the study and r and omly divided into two groups . The first group received amitriptyline and the second citalopram for 16 weeks . Patients were assessed at weeks 0 , 4 , 8 , and 16 . The two drugs were equally efficacious in relieving depressive symptoms , although amitriptyline was more efficacious than citalopram in reducing migraine and TTH attacks . Patients who did not respond to monotherapy ( < 30 % of improvement in the clinical scores ) were treated with a combination of the two drugs for 16 additional weeks . In these selected patients , the combined treatment produced a substantial improvement in depression , migraine and TTH without producing major side effects such as those commonly related to the ‘ serotonergic ’ syndrome . The results indicate that a combined therapy with amitriptyline and citalopram may be particularly beneficial for patients with TTH , migraine and comorbid depression that do not respond to monotherapy
target: Two studies compared SSRIs or SNRIs versus amitriptyline and found no evidence for a difference in terms of migraine frequency ( st and ardised mean difference ( SMD ) 0.04 , 95 % confidence interval ( CI ) -0.72 to 0.80 ; I(2 ) = 72 % ) , or other secondary outcomes such as migraine intensity and duration .SSRIs  or SNRIs were generally more tolerable than tricyclics .
  Since the last version of this review , the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine as preventive drugs for migraine .
  There is no evidence to consider SSRIs or venlafaxine as more effective than placebo or amitriptyline in reducing migraine frequency , intensity , and duration over two to three months of treatment .
  Our conclusion is that the use of SSRIs and SNRIs for migraine prophylaxis is not supported by evidence
background: BACKGROUND This is an up date d version of the original Cochrane review published in 2005 on selective serotonin reuptake inhibitors ( SSRIs ) for preventing  migraine and tension-type headache .
  Another up date d review is under development to cover tension-type headache .
  Migraine is a common disorder .
  The chronic forms are associated with disability and have a high economic impact .
  In view of discoveries about the role of serotonin and other neurotransmitters in pain mechanisms , selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-norepinephrine reuptake inhibitors ( SNRIs ) have been evaluated for the prevention of migraine .
  OBJECTIVES To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic migraine in adults .