Sertraline in chronic tension-type headache. Chronic tension-type headache, mood depression and serotonin: therapeutic effects of fluvoxamine and mianserine. Antidepressant treatment of chronic tension-type headache: a comparison between fluoxetine and desipramine. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. Selective serotonin reuptake inhibitors for migraine prophylaxis. Sertraline versus amitriptyline in the prophylactic therapy of non-depressed chronic tension-type headache patients A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache. Efficacy of single versus three sessions of high rate repetitive transcranial magnetic stimulation in chronic migraine and tension-type headache Psychotherapy versus usual care in pediatric migraine and tension-type headache: a single-blind controlled pilot study Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial. Cognitive behavior therapy for comorbid migraine and/or tension-type headache and major depressive disorder: An exploratory randomized controlled trial. Systematic review of cognitive behavioural therapy for the management of headaches and migraines in adults Relaxation Training and Written Emotional Disclosure for Tension or Migraine Headaches: A Randomized, Controlled Trial The Natural History of Headache: Predictors of Onset and Recovery Increased brain GABA concentrations following acute administration of a selective serotonin reuptake inhibitor. Recurrent tension headache in adolescents treated with self-help relaxation training and a muscle relaxant drug. Effectiveness of a Treatment Involving Soft Tissue Techniques and/or Neural Mobilization Techniques in the Management of Tension-Type Headache: A Randomized Controlled Trial.
OBJECTIVES To study the effect of Sertraline , a selective serotonin reuptake inhibitor in  chronic tension type headache ( CTTH ) in a double blind placebo controlled r and omized trial . MATERIAL AND METHODS The study design was a double blind placebo controlled r and omized study of 50 patients , over a period of 10 weeks including run-in period of two weeks , treatment period four weeks , and follow-up four weeks . The diagnosis of CTTH was based on criteria given by International Headache Society ( IHS ) . The overall response was grade d in terms of headache index , analgesic intake per week and percentage reduction in headache frequency using chi-square and ' t ' test . Anxiety and depression was assessed using Hamilton Rating Scale . RESULTS The mean analgesic intake per week declined from 4.34 + /- 0.736 tab/week to 1.07 + /- 0.592 tab/week in sertraline group ( p < 0.01 ) while reduction in placebo group was not significant ( 3.98 + /- 0.729 tab/week to 2.94 + /- 0.665 tab/week ) ( p > 0.05 ) . The reduction in headache index and percentage reduction in frequency of headache was not significant in drug treatment group . Side effects were seen in 24.4 % of patients nausea , nervousness and dizziness being the commonest . CONCLUSION The drug treatment group showed a significant decline in analgesic intake per week . The study result shows that sertraline can be a useful alternative to amitryptiline in those patients who fail to respond or can not tolerate it 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 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 Serotonin ( 5-HT ) plays a crucial role in mediating the descending pain inhibitory systems and in the pathophysiology of migraine . Previous studies regarding the use of 5-Hydroxytryptophan ( 5-HTP ) , the active precursor of 5-HT , in the treatment of Chronic Primary Headache ( CPH ) have been inconclusive so far . In order to assess the efficacy of the serotonin active precursor in chronic headache prophylaxis , a double-blind cross-over study has been carried out in 31 patients with CPH , comparing L-5-HTP to placebo . Clinical syndromes included : ( a ) migraine ( 16 patients ) ; ( b ) mixed headache ( 6 patients ) ; ( c ) psychogenic headache ( 5 patients ) ; ( d ) muscle contraction headache ( 4 patients ) .  L-5-HTP was administered for two months at daily doses of 400 mg p.o . The reduction in severity and frequency of headache in patients taking the active drug and placebo was noted . Mood patterns were also taken into consideration . L-5-HTP proved to be more effective than placebo in reducing both headache frequency and severity , but the difference was not statistically significant . Favourable responses ( greater than 50 % average reduction in headache symptoms ) were obtained in 48 % of the cases after the second month of treatment . No significant difference in therapeutic response was observed as related to different clinical syndromes , except for psychogenic headache patients , who responded poorly to the active drug . Side effects , experienced in 19 % of the cases , were generally mild and transient . We conclude that L-5-HTP is a medication of moderate efficacy and remarkable safety , providing us with another alternative approach to CPH prophylaxis 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 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 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 We report the efficacy of three versus single session of 10 Hz repetitive transcranial magnetic stimulation ( rTMS ) in  chronic migraine ( CM ) and chronic tension-type headache ( CTTH ) . Ninety-eight patients with CM or CTTH were included and their headache frequency , severity , functional disability and number of abortive medications  were noted . Fifty-two patients were r and omly assigned to group I ( three true sessions ) and 46 to group II ( one true and two sham rTMS sessions ) treatment . 10 Hz rTMS comprising 600 pulses was delivered in 412.4 s on the left frontal cortex . Outcomes were noted at 1 , 2 and 3 months . The primary outcome was 50 % reduction in headache frequency , and secondary outcomes were improvement in severity , functional disability , abortive drugs and side effects . The baseline headache characteristics were similar between the two groups . Follow up at different time points revealed significant improvement in headache frequency , severity , functional disability and number of abortive drugs compared to baseline in both group I and group II patients , although these parameters were not different between the two groups . In group I , 31 ( 79.4 % ) had reduction of headache frequency and 29 ( 74.4 % ) converted to episodic headache . In group II , these were 24 ( 64.8 % ) and 22 ( 59.2 % ) , respectively . In chronic migraine , the severity of headache at 2 months reduced in group I compared to group II ( 62.5 vs 35.3 % ; P = 0.01 ) . Both single and three sessions of 10 Hz rTMS were found to be equally effective in CM and CTTH , and result ed in conversion of chronic to episodic headache in 67.1 % patients Background Despite growing interest in psychotherapy in child and adolescent headache , efficacy studies in this research field have focused mainly on cognitive-behavioral therapies . Whereas relaxation and cognitive-behavioral techniques , in particular , have been found to reduce the intensity and frequency of headache in children and adolescents , data on psychodynamic psychotherapy in this population are lacking . Our aim was to explore the effectiveness of a brief psychodynamic psychotherapy program in the treatment of idiopathic headache in childhood and adolescence . Methods Thirty-three newly diagnosed idiopathic headache sufferers aged 6–18 years , consecutively referred to our outpatient services , were r and omized to receive either a brief cycle of psychodynamic psychotherapy ( eight sessions administered at two-week intervals ) or usual care ( clinical interview , neurological examination , counselling , symptomatic therapy).The two groups were evaluated at baseline ( T0 ) and at six months ( T1 ) to be assessed for headache characteristics ( i.e. frequency , intensity and duration ) , quality of life ( i.e. the EuroQoL score ) , patient ’s global health status ( i.e. the Clinical Global Impression score ) , and emotional-behavioral symptoms ( i.e. Child Behavior Checklist scores ) . Results The two groups were fairly similar with reference to the main demographic and clinical variables . The T0/T1 comparison showed a statistically significant improvement in headache frequency ( p = 0.005 ) , intensity ( p < 0.001 ) and duration ( p = 0.002 ) , a statistically significant improvement in the CGI score ( p = 0.018 ) , and a borderline improvement in the EuroQoL score ( p = 0.053 ) in the group receiving psychotherapy . Conclusions According to our pilot findings , a brief psychodynamic psychotherapy program may be more effective than usual care in children and adolescents with idiopathic headache CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice . Behavioral and pharmacological therapies each appear modestly effective , but data are lacking on their separate and combined effects . OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies , singly and combined , for chronic tension-type headaches . DESIGN AND SETTING R and omized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio . PARTICIPANTS Two hundred three adults ( mean age , 37 years ; 76 % women ) with diagnosis of chronic tension-type headaches ( mean , 26 headache d/mo ) . INTERVENTIONS Participants were r and omly assigned to receive tricyclic antidepressant ( amitriptyline hydrochloride , up to 100 mg/d , or nortriptyline hydrochloride , up to 75 mg/d ) medication ( n = 53 ) , placebo ( n = 48 ) , stress management ( eg , relaxation , cognitive coping ) therapy ( 3 sessions and 2 telephone contacts ) plus placebo ( n = 49 ) , or stress management therapy plus antidepressant medication ( n = 53 ) . MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings ( 0 - 10 scale ) recorded by participants in a daily diary 4 times per day ; number of days per month with at least moderate pain ( pain rating > /=5 ) , analgesic medication use , and Headache Disability Inventory scores , compared by intervention group . RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity , analgesic medication use , and headache-related disability than placebo , but antidepressant medication yielded more rapid improvements in headache activity . Combined therapy was more likely to produce clinical ly significant ( > /=50 % ) reductions in headache index scores ( 64 % of participants ) than antidepressant medication ( 38 % of participants ; P = .006 ) , stress management therapy ( 35 % ; P = .003 ) , or placebo ( 29 % ; P = .001 ) . On other measures the combined therapy and its 2 component therapies produced similar outcomes . CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches . Combined therapy may improve outcome relative to monotherapy Numerous studies have demonstrated comorbidity between migraine and tension-type headache on the one h and , and depression on the other . Presence of depression is a negative prognostic indicator for behavioral treatment of headaches . Despite the recognised comorbidity , there is a limited research literature evaluating interventions design ed for comorbid headaches and depression . Sixty six participants ( 49 female , 17 male ) suffering from migraine and /or tension-type headache and major depressive disorder were r and omly allocated to a  Routine Primary Care control group or a Cognitive Behavior Therapy group that also received routine primary care . The treatment program involved 12 weekly 50-min sessions administered by clinical psychologists . Participants in the treatment group improved significantly more than participants in the control group from pre-to post-treatment on measures of headaches , depression , anxiety , and quality of life . Improvements achieved with treatment were maintained at four month follow-up . Comorbid anxiety disorders were not a predictor of response to treatment , and the only significant predictor was gender ( men improved more than women ) . The new integrated treatment program appears promising and worthy of further investigation Aim : This systematic review aim ed to establish if cognitive behavioural therapy ( CBT ) can reduce the physical symptoms of chronic headache and migraines in adults . Methods : Evidence from search es of eight data bases was systematic ally sought , appraised and synthesis ed . Screening of title and abstract s was conducted independently by two review ers . Full papers were screened , data extracted and quality assessed by one review er and checked by a second . Data were synthesis ed narratively by intervention due to the heterogeneity of the studies . The inclusion criteria specified r and omised controlled trials with CBT as an intervention in adults suffering from chronic headaches/migraines not associated with an underlying pathology/medication overuse .  CBT was judged on the basis of authors describing the intervention as CBT . The diagnosis of the condition had to be clinician verified . Studies had to include a comparator and employ headache/migraine-specific outcomes such as patient-reported headache days . Results : Out of 1126 screened titles and abstract s and 20 assessed full papers , 10 studies met the inclusion criteria of the review . Some studies combined CBT with another intervention , as well as employing varying numbers of comparators . CBT was statistically significantly more effective in improving some headaches-related outcomes in CBT comparisons with waiting lists ( three studies ) , in combination with relaxation compared with relaxation only ( three studies ) or antidepressant medication ( one study ) , with no statistically significant differences in three studies . Conclusions : The findings of this review were mixed , with some studies providing evidence in support of the suggestion that people experiencing headaches or migraines can benefit from CBT , and that CBT can reduce the physical symptoms of headache and migraines . However , methodology inadequacies in the evidence base make it difficult to draw any meaningful conclusions or to make any recommendations Background and Purpose Behavioral medicine interventions that directly reduce arousal and negative emotions , such as relaxation training ( RT ) , are conceptually different from interventions that temporarily increase negative emotions , such as written emotional disclosure ( WED ) , but no studies have directly compared their efficacy . We compared the effects of RT and WED on people with tension or migraine headaches . Methods College students with either tension ( n = 51 ) or migraine ( n = 90 ) headaches were r and omized to one of three groups : RT , WED , or a neutral writing control condition ; four sessions were held over 2 weeks . Mood was measured before and after each session , and outcomes ( headache frequency , severity , disability , and general physical symptoms ) were assessed at baseline and at 1-month and 3-month follow-ups . Results As expected , RT led to an immediate increase in calmness , whereas WED led to an immediate increase in negative mood , for both headache sample s. Intent-to-treat analyses showed that , for the tension headache sample , RT led to improved headache frequency and disability compared to both WED and the control group , but WED had no effect . For migraine headaches , RT improved pain severity relative to the control group , but WED again had no effect . Conclusions A brief RT protocol was effective for tension headaches , but WED had no effect on health status for either tension or migraine headaches . Modifications to WED , such as targeting people with unresolved stress , providing guidance to enhance the potency of the writing , or including additional at-home writing and exposure exercises , may improve its efficacy for people with headaches and other health problems The objective of this study was to determine predictors of onset of new headache episodes and recovery from headache over one year . A population -based cohort study was conducted , comprising a baseline postal survey to a r and om sample of adults aged ≥18 years , with follow-up survey after 1 year . Risk factor data at baseline were compared with headache status at follow-up in two groups : ( i ) those free of recent headache at baseline and ( ii ) those with a recent headache at baseline . In respondents free of recent headache at baseline , previous headache [ risk ratio ( RR ) 4.15 ] , the presence of other pain at baseline ( RR 1.43 ) , severe sleep problems ( RR 1.67 ) and drinking caffeine ( RR 1.99 ) increased the risk of a new headache episode during the follow-up year . In respondents with recent headache at baseline , less severe headaches at baseline predicted recovery during the follow-up year , as did the absence of anxiety [ recovery ratio ( ReR ) 2.84 ] and of sleep problems ( ReR 2.77 ) . Risks for increased headache-related disability reflected those for onset of a new episode and these risks increased in strength for large increases in disability .  Sleep problems and caffeine consumption increase the risk of developing headache and thus provide targets for prevention . Low levels of anxiety , sleep problems and the absence of other pain improve the likelihood of recovering and remaining free from headache OBJECTIVE The authors used magnetic resonance spectroscopy ( MRS ) to assess the effect of acute administration of the selective serotonin reuptake inhibitor ( SSRI ) citalopram on cortical levels of gamma-aminobutyric acid ( GABA ) . METHOD Ten healthy volunteers received either intravenous citalopram ( 10 mg ) or saline in a r and omized , double-blind , crossover design . The occipital GABA/creatine ratio was measured with a proton MR spectral editing technique . RESULTS In comparison with saline , citalopram produced a mean increase of 35 % in relative brain GABA concentration in the occipital cortex . CONCLUSIONS These findings extend previous work showing that SSRI treatment increases cortical GABA in depressed patients and suggest that this results from an action of SSRIs on GABA neurons rather than as a secondary consequence of mood improvement Forty-eight adolescents suffering from recurrent tension headache participated in a controlled trial conducted in a high school setting . During the first treatment phase self-help relaxation training was compared with a waiting-list group . Following this phase a pharmacological regimen consisting of a muscle relaxant ( chlormezanone ) and placebo was superimposed on relaxation therapy in a double-blind crossover design . Each treatment phase encompassed a 5-week period . In addition to the evaluation of headache complaints , psychological distress among students  was measured with respect to their experience of somatic complaints , depressive , anxiety and stress symptoms . Although self-help relaxation training significantly decreased the severity and annoyance of adolescents ' headache besides their somatic complaints , the clinical improvement of headache was modest . The addition of chlormezanone did not help those who were nonresponders to self-help relaxation training . Finally , a set of pretreatment variables consisting of baseline headache severity and annoyance , experience of anxiety and daily life stress among adolescents could predict outcome of self-help relaxation therapy OBJECTIVE To evaluate the effects of a protocol involving soft tissue techniques and /or neural mobilization techniques in the management of patients with frequent episodic tension-type headache ( FETTH ) and those with chronic tension-type headache ( CTTH ) . DESIGN R and omized , double-blind , placebo-controlled before and after trial . SETTING Rehabilitation area of the local hospital and a private physiotherapy center . PARTICIPANTS Patients ( N=97 ; 78 women , 19 men ) diagnosed with FETTH or CTTH were r and omly assigned to groups A , B , C , or D. INTERVENTIONS ( A ) Placebo superficial massage ; ( B ) soft tissue techniques ; ( C ) neural mobilization techniques ; ( D ) a combination of soft tissue and neural mobilization techniques . MAIN OUTCOMES MEASURES The pressure pain threshold ( PPT ) in the temporal muscles ( points 1 and 2 ) and supraorbital region ( point 3 ) , the frequency and maximal intensity of pain crisis , and the score in the Headache Impact Test-6 ( HIT-6 ) were evaluated . All variables were assessed before the intervention , at the end of the intervention , and 15 and 30 days after the intervention . RESULTS Groups B , C , and D had an increase in PPT and a reduction in frequency , maximal intensity , and HIT-6 values in all time points after the intervention as compared with baseline and group A ( P<.001 for all cases ) . Group D had the highest PPT values and the lowest frequency and HIT-6 values after the intervention . CONCLUSIONS The application of soft tissue and neural mobilization techniques to patients with FETTH or CTTH induces significant changes in PPT , the characteristics of pain crisis , and its effect on activities of daily living as compared with the application of these techniques as isolated interventions
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 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 .