title: A comparative study of amitriptyline and fluvoxamine in migraine prophylaxis. Fluoxetine for migraine prophylaxis: a double-blind trial. Sertraline versus amitriptyline in the prophylactic therapy of non-depressed chronic tension-type headache patients Antidepressant treatment of chronic tension-type headache: a comparison between fluoxetine and desipramine. Sulpiride and Paroxetine in the Treatment of Chronic Tension‐Type Headache. An Explanatory Double‐Blind Trial EFNS guidelines on pharmacological treatment of neuropathic pain A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache. Amitriptyline Versus Amitriptyline Combined With Fluoxetine in the Preventative Treatment of Transformed Migraine: A Double‐Blind Study Chronic tension-type headache, mood depression and serotonin: therapeutic effects of fluvoxamine and mianserine. Double‐Blind Trial of Fluoxetine: Chronic Daily Headache and Migraine Fluoxetine prophylaxis of migraine. The economic burden of headache: an epidemiological study in the Republic of San Marino. Femoxetine in the prophylaxis of migraine ‐ A randomised comparison with placebo Paroxetine in the Treatment of Chronic Daily Headache Selective serotonin reuptake inhibitors for migraine prophylaxis. A randomized general practice * group‐comparative study of femoxetine and placebo in the prophylaxis of migraine Migraine and reduced work performance Propranolol and femoxetine, a HT-uptake inhibitor, in migraine prophylaxis. A double-blind crossover study.
abstract: 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 Abstract Patients with chronic tension- type headache ( CTTH ) are the most difficult to treat . Tricyclic antidepressants are the first-line therapeutic agents , but their anticholinergic side effects limit their usage . Selective serotonin reuptake inhibitors ( SSRI ) with fewer side effects than tricyclic antidepressants have also been used in treatment of CTTH , but the results are conflicting . In this study , prophylactic action of sertraline in treatment of nondepressed patients with CTTH was investigated and compared with amitriptyline in a prospect i ve , r and omized , open label , parallel-group study . A 4-week baseline period was followed by a 12-week treatment period with either 50 mg sertraline  ( n=41 patients ) or 25 mg amitriptyline  ( n=44 patients ) . Efficacies of treatments were determined by using a headache diary , in which patients recorded the occurrence , number , intensity and duration of headaches in days , analgesic drug consumption and any adverse events . Both drugs reduced headache symptoms and analgesic drug consumption at the first , second and third months of treatment compared to baseline values . There was significant superiority of amitriptyline in the headache symptoms and drug consumption reductions versus sertraline at the second and third months of treatment . Side effects were more favorable in the sertraline-treated patients , but dropouts were similar in both groups . These results suggest that both drugs were effective in the treatment of non-depressed patients with CTTH , but in comparison between groups , amitriptyline was more effective than sertraline Amitriptyline , which is a noradrenaline reuptake and 5-HT reuptake inhibitor , has an established role in the management of  chronic tension-type headaches .  In a single-blind study , patients with chronic tension-type headache were r and omized to either fluoxetine 20 mg ( a selective 5-HT reuptake inhibitor ) or desipramine 75 mg ( a selective noradrenaline reuptake inhibitor ) and followed for 12 weeks to compare the effectiveness of the two drugs in improving headache , and to assess whether pain control is related to changes in depression . Patients were evaluated at weekly intervals on an analog pain-rating scale and at 4-weekly intervals on the Montgomery and Asberg Depression Rating Scale ( MADRS ) , the MOS general health status question naire ( SF36 ) , the Hospital Anxiety and Depression Scale ( HADS ) , and a side effects checklist .  Eighteen patients were r and omized to take fluoxetine and 19 to take desipramine . Of the 25 patients who completed the trial , 12 were on  fluoxetine and 13 were on desipramine . There was no significant difference between the two groups at baseline nor in change of pain ; reduction in use of analgesic medication ; nor change in the HADS , MADRS , or SF36 scores at 12 weeks , but 72 % of patients who completed the study improved , and this improvement almost exactly mirrored the improvement on the MADRS . The results from this trial are compatible with the notion that the beneficial effect of antidepressants in  chronic tension-type headache  is indirect , mediated by an effect on depression , and not more , dependent on serotonin reuptake inhibition than noradrenaline reuptake inhibition SYNOPSIS Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials . This EFNS Task Force aim ed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain . Studies were identified using first the Cochrane Data base then Medline . Trials were classified according to the aetiological condition . All class I and II controlled trials ( according to EFNS classification of evidence ) were assessed , but lower‐class studies were considered in conditions that had no top level studies . Only treatments feasible in an outpatient setting were evaluated . Effects on pain symptoms/signs , quality of life and comorbidities were particularly search ed for . Most of the r and omized controlled trials included patients with postherpetic neuralgia ( PHN ) and painful polyneuropathies ( PPN ) mainly caused by diabetes . These trials provide level A evidence for the efficacy of tricyclic antidepressants , gabapentin , pregabalin and opioids , with a large number of class I trials , followed by topical lidocaine ( in PHN ) and the newer antidepressants venlafaxine and duloxetine ( in PPN ) . A small number of controlled trials were performed in central pain , trigeminal neuralgia , other peripheral neuropathic pain states and multiple‐aetiology neuropathic pains . The main peripheral pain conditions respond similarly well to tricyclic antidepressants , gabapentin , and pregabalin , but some conditions , such as HIV‐associated polyneuropathy , are more refractory . There are too few studies on central pain , combination therapy , and head‐to‐head comparison . For future trials , we recommend to assess quality of life and pain symptoms or signs with st and ardized tools OBJECTIVES : Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache , only few studies have investigated the efficacy of this treatment and the results are contradictory . In addition , the new selective serotonin reuptake inhibiting antidepressants , which are widely used in depression and of potential value in pain management , have never been investigated in a placebo controlled study of tension-type headache . The aim was to evaluate the efficacy of amitriptyline and of the selective serotonin reuptake inhibitor citalopram in chronic tension-type headache . METHODS : Forty non-depressed patients with chronic tension type headache were included in a 32 week , double blind , placebo controlled , three-way crossover study . RESULTS : Thirty four patients completed the trial .  Amitriptyline reduced area under the headache curve by 30 % compared with placebo ( P = 0.002 ) , whereas citalopram had no significant effect ( P = 0.68 ) . Explanatory analyses showed that amitriptyline significantly reduced the duration of headache ( P = 0.01 ) , headache frequency ( P = 0.01 ) , and intake of analgesics ( P = 0.02 ) but not headache intensity ( P = 0.12 ) . CONCLUSION : Although amitriptyline did not eliminate the headache , it provided a clinical ly important reduction of headache in the majority of otherwise treatment resistant patients . The differential effect of amitriptyline and citalopram indicates that mechanisms other than inhibition of serotonin reuptake are involved in the analgesic effect of the tricyclic antidepressants . Amitriptyline , but not citalopram , is valuable in the prophylactic treatment of chronic tension type headache Background 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 Forty out- patients affected by chronic tension-type headache were selected according to the diagnostic criteria of International Headache Society ( IHS ) Headache Classification Committee . In a controlled trial patients received placebo for a four-week baseline period , then they were r and omized in double-blind fashion to therapy with mianserine ( 30 - 60 mg/day ) of fluvoxamine ( 50 - 100 mg/day ) for another eight-week period . Frequency of headache , pain severity and analgesic consumption were evaluated using a self-monitoring system . Mood depression was evaluated at 0 , 4 and 8 weeks by using Zung 's Self-Rating Depression Scale and Hamilton Rating Scale for Depression . Both drugs were beneficial in the treatment of chronic tension-type headache .  Non-depressed subjects with more severe headache responded best to fluvoxamine , whereas mianserine was more effective in the treatment of depressed patients with moderate headache . These results suggest that central serotoninergic neurotransmission can play a role in the pathophysiology of chronic tension-type headache also in non-depressed patients 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 SYNOPSIS We examined the socio-economic consequences of headache in a r and om sample of 514 working people living inthe Republic of San Marino . Our results show that , in the preceding year , 255 out of 514 ( 49.6 % ) suffered fromheadache ; 31.9 % ( 164/514 ) reported decreased efficiency as a consequence of headache ; 9.3 % ( 48/514 ) reportedthat head pain is always severe ; 7.4 % ( 38/514 ) were absent from work because of headache for a total of 338working days lost ; 8.4 % of all working days lost to illness were due to headache . We estimated that in the Republic of San Marino ( 21,792 inhabitants ) , headache causes a loss of at least 5,000working days every year . Since the cost of a working day in the Republic of San Marino is about 100,000 italianlire , the economic burden in this area amounts to 500 millions of lire in a year . This shows that headache is amajor socio-medical problem 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 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 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 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
target: Over 2 months of treatment , SSRIs are no more efficacious than placebo in patients with migraine .
  In patients with chronic TTH , SSRIs are less efficacious than tricyclic antidepressants .
  In comparison with SSRIs , the burden of adverse events in patients receiving tricyclics was greater .
background: BACKGROUND Headache is a common medical problem .
  In view of recent discoveries about the role of serotonin in pain mechanisms , selective serotonin re-uptake inhibitors ( SSRIs ) have been evaluated for the prevention of  migraine and tension-type headaches ( TTH ) .
  OBJECTIVES To evaluate the efficacy and tolerability of SSRIs for preventing migraine and TTH .