Tension-type headache in adults: Preventive treatment

INTRODUCTION — 

Tension-type headache (TTH) is characterized by a bilateral, nonthrobbing headache of a mild to moderate intensity, typically without other associated features. TTH is the most common headache and prevalent neurologic disorder in the population. Due to its high prevalence, TTH is associated with a high overall burden of disability in the population.

The preventive therapies of TTH in adults are reviewed here. Other aspects of TTH are discussed separately.

●(See "Tension-type headache in adults: Etiology, clinical features, and diagnosis".)

●(See "Tension-type headache in adults: Acute treatment".)

●(See "Tension-type headache in children".)

INDICATIONS FOR PREVENTIVE TREATMENT — 

Prophylactic headache treatment is indicated if the headaches are frequent, long lasting, or are disabling [1]. This may include patients with any of the following TTH features [2]:

●frequency ≥2 headache days each week,

●duration ≥4 hours, or poorly responsive to acute therapies, OR

●severity that impairs functioning (disabling).

Preventive therapy is typically indicated for most patients with both the frequent episodic TTH subtype (1 to 14 headache days a month) and chronic TTH subtype (≥15 headache days a month).

Many patients with TTH who have up to 10 headache days per month can manage headaches with acute therapies, such as acetaminophen and nonsteroidal anti-inflammatory drugs. However, frequent use of acute therapies alone may indicate inadequate response to treatment, expose the patient to a higher risk of adverse events, and increase the potential for medication overuse headache. Adding preventive strategies for these patients with frequent TTH may reduce reliance on acute therapies, better ameliorate the overall symptoms of TTH, and cotreat associated comorbid conditions (eg, depression and anxiety).

Patients with infrequent episodic TTH (<1 headache days per month) are typically managed with acute therapies alone. (See "Tension-type headache in adults: Acute treatment".)

Goals of treatment — The goals of preventive therapy in TTH are extrapolated from those devised for migraine headache and include [1]:

●Reduce attack frequency, severity, and duration

●Improve responsiveness to treatment of acute attacks

●Improve function and reduce disability

OUR APPROACH — 

For most patients with TTH, we start with nonpharmacologic therapies such as biofeedback and relaxation therapy, stress and headache trigger management, or other specific interventions. For patients with severe symptoms and those who prefer pharmacotherapy, we use or add preventive medications for TTH (algorithm 1). For some patients, TTH may be difficult to treat, but an acceptable result can usually be obtained by nonpharmacologic interventions, pharmacologic therapy, or a combination of nonpharmacologic and pharmacologic modalities [3].

Pretreatment counseling — To best achieve benefit, prophylactic headache therapy requires a sustained commitment on the part of the patient and clinician [4]. It is important to address patient expectations and consider patient preferences when deciding between different preventive therapies. In addition, the patient should be informed of the rationale for a particular treatment, the expected benefits of therapy, the duration of treatment that will likely be needed to achieve improvement, and possible adverse effects.

A stress-reducing therapeutic benefit may also be attained simply by taking the problem seriously, particularly if the patient is worried that the headache is caused by a serious problem such as a brain tumor. The evaluation of TTH is discussed separately. (See "Tension-type headache in adults: Etiology, clinical features, and diagnosis", section on 'Diagnostic testing'.)

Selection of therapies — The selection of preventive TTH treatment strategies should be individualized. Some patients with TTH attacks that are frequent, prolonged, and/or severe who prioritize efficacy of initial management may select medications along with nonpharmacologic therapies, while others who wish to avoid medications may prefer nonpharmacologic interventions alone. Other patients who are unwilling or unable to comply with nonpharmacologic protocols may elect to start with pharmacologic treatments alone.

Many patients who present for management of TTH have disabling symptoms, warranting a trial of pharmacotherapy along with nonpharmacologic management, even though the scientific evidence for this approach is sparse and contradictory [2]. Limited trial data suggest a strategy of nonpharmacologic therapy plus medications may be more effective than either option alone [5]. (See 'Combination tricyclic and behavioral therapy' below.)

A nonpharmacologic approach may be particularly well-suited for patients with the following features [6]:

●Lower burden of headache symptoms

●History of excessive use of analgesics or acute medications

●Insufficient response to, or poor tolerance of, pharmacologic treatments

●Significant stress or modifiable headache triggers (eg, sleep disturbance, dehydration)

●Pregnancy (or planning to become pregnant) or nursing

●Preference to avoid pharmacologic treatment

Pharmacologic treatment principles — Benefits of pharmacotherapy for TTH prevention are often delayed while the medication is titrated to an effective dose, and effectiveness may be partial or achieved after trials of multiple medications. Commitment from both patient and clinician as well as an understanding of the goals of therapy are required to optimize efficacy of TTH pharmacotherapy. Our general approach to guide pharmacotherapy for TTH includes:

●Slow titration – Start the drug at the lowest dose and increase gradually until therapeutic benefit is achieved, the maximum dose of the drug is reached, or adverse effects become intolerable.

●Duration of treatment – Give the prophylactic medication an adequate trial in terms of duration and dose. Benefit is often first noted after four to six weeks of therapy [7,8]. In addition, benefit may continue to accrue for three or more months. Once an effective regimen is identified, maintain drug therapy for at least three to six months. Thereafter, a slow taper can be attempted [7]. The regimen can be resumed if symptoms relapse.

●Avoid overuse of acute therapies – Avoid overuse of analgesic medications. Ongoing analgesic overuse must be eliminated, or preventive therapy will likely be ineffective.

●Monitoring – Measure the effectiveness of therapy by use of a patient headache diary to track daily headache frequency and intensity. Schedule periodic clinical evaluations to assess efficacy and monitor for adverse effects.

INITIAL THERAPY

Behavioral therapies — For most patients with TTH, we suggest initial treatment with a behavioral therapy. Biofeedback combined with relaxation therapy has the best evidence of efficacy; alternatives include biofeedback or relaxation therapy alone, self-management, and cognitive-behavioral therapy.

The goal of behavioral treatments is to prevent headaches by identifying and defusing headache triggers [9]. Behavioral therapies can target specific headache triggers, and several modalities have been shown to modestly reduce headache burden in multiple studies [10]. Epidemiologic studies suggest that stress and mental tension are the most frequently identified triggers for TTH [11]. Since there is an important behavioral component to nearly all of the known headache triggers, behavioral therapies are a potentially useful means of coping with and/or alleviating these triggers [6]. Coping with headache triggers is probably a more valuable strategy than advice to avoid the triggers for most patients [12]. For example, stretching and exercises may help when neck movements trigger TTH, and periodic breaks may help when eye strain from computer use trigger symptoms.

Behavioral treatments for TTH include [6,9,13]:

●Biofeedback

●Relaxation

●Self-regulation of sleep, exercise, stress, and other triggers

●Cognitive-behavioral therapy

●Combinations of the above therapies

Biofeedback with relaxation therapy — We suggest treatment using biofeedback combined with relaxation therapy rather than other behavioral therapy options for initial nonpharmacologic management of patients with frequent episodic TTH or chronic TTH. This recommendation is similar to the conclusions of the 2010 European guidelines for the treatment of TTH, which reported biofeedback for TTH can have a substantial effect that may be enhanced by added relaxation therapy, but the evidence to support an effect of cognitive-behavioral therapy and relaxation training alone is uncertain [2].

●Biofeedback – Biofeedback methods are based upon the notion that an individual can learn to control involuntary and subconscious physiologic processes when information about these processes is fed back in the form of a visual or auditory signal [9].

Pericranial muscle tenderness is often associated with TTH, but many patients are either not aware of the relationship or overly fixate on its importance. Biofeedback may be helpful in either circumstance. Patients are typically trained over several guided sessions to recognize focal muscle tension and then to practice controlling muscle activation. Electromyography feedback is the predominant method used in TTH treatment.

●Relaxation therapy – Relaxation techniques are based upon the premise that an unwanted outcome, such as headache, can be diminished or avoided by altering physiologic responses and decreasing sympathetic arousal [9]. Various forms of relaxation include progressive muscle relaxation, autogenic training (ie, learning self-statements that suggest warmth and heaviness), meditative or passive relaxation, and self-hypnosis.

Relaxation therapy is often begun with a guided introduction and training but may be continued by self-direction for ongoing use. It may be performed alone or together with other therapies such as biofeedback.

Trial data assessing comparative effects of different behavioral therapies are limited. A 2008 meta-analysis of biofeedback for TTH included 53 studies and concluded that biofeedback was more effective than headache monitoring, placebo, and relaxation therapies [14]. Biofeedback was associated with a moderate to large effect on headache relief compared with pretreatment baseline (mean weighted effect 0.73, 95% CI 0.61–0.84). In addition, this effect was long-lasting (follow-up 3 to 60 months) and enhanced by combination with relaxation therapy. However, a 2009 review of randomized trials evaluating different behavioral treatments for chronic TTH included 44 trials with 2618 patients, but outcome measures varied, and results were inconsistent [10]. In 11 studies, biofeedback was compared with waitlist conditions, and in eight studies, relaxation treatment was compared with waitlist conditions, both showing inconsistent results. Most trials lacked adequate statistical power, and rates of recovery or improvement frequently failed to reach clinical relevance.

Alternative options — For patients with TTH using nonpharmacologic therapy who have an inadequate response to biofeedback with relaxation therapy, we switch to or add alternative nonpharmacologic options. We also use alternative behavioral options for patients unwilling or unable to comply with biofeedback and/or relaxation protocols.

Self-management — Self-management is a behavioral paradigm for TTH management that involves developing knowledge of headache triggers with attention to reducing any identified trigger. This process includes addressing:

●Sleep disturbances,

●Insufficient exercise,

●Medication (and caffeine) overuse,

●Stress related to life events, AND

●Any other identified triggers (eg, neck movements, dehydration, sunlight exposure).

Triggers may be reported by patients with an established pattern of TTH, elicited during clinical evaluation, or identified with the use of a headache diary. (See "Tension-type headache in adults: Etiology, clinical features, and diagnosis", section on 'Clinical features'.)

The emphasis of self-management is focused on developing stress awareness and control. Supportive self-management approaches require collaboration between patient and clinician but rely on a high degree of patient self-engagement in health promotion, which can promote long-term benefit but may limit its utility for some patients [6]. This approach may be appealing as an accessible, low-risk strategy for TTH prevention, especially for patients with infrequent headaches.

Data on the effectiveness of self-management for TTH are limited, but some studies suggest it may help reduce symptom burden or evolution from episodic to chronic TTH [6]. In a systematic review of 16 trials that included patients with either TTH or migraine, self-management strategies had modest beneficial effects on pain intensity, headache-related disability, medication use, and mood but did not reduce headache frequency [15]. However, certainty in these results is limited by heterogeneity of patient populations and specific self-management strategies, inclusion of patients with migraine, and risk of bias due to nonblinded outcome assessments in some studies.

Stress management plus pharmacotherapy with tricyclic antidepressants may be more effective than behavioral therapy alone. (See 'Combination tricyclic and behavioral therapy' below.)

Cognitive-behavioral therapy — Cognitive-behavioral therapy may be used in patients with triggers for TTH by attempting to modify the response to headache triggers by altering the usual interpretations, thoughts, and assumptions associated with such events [9]. Cognitive-behavioral therapy combines principles of cognitive therapy, which teaches patients to identify, evaluate, and better respond to their dysfunctional thoughts and beliefs, and behavior therapy, which helps patients develop new and adaptive ways of behaving.

Cognitive-behavioral therapy is led by a therapist trained in the technique. Patients are taught to identify headache triggers (whether physical, psychologic, or behavioral) and develop effective (cognitive or behavioral) corrective or coping strategies to disrupt the relationship between trigger and subsequent headache.

Limited data suggest cognitive-behavioral therapy may be helpful for some patients with TTH [5,10]. In a trial of 203 patients with chronic TTH who were treated with pharmacotherapy, cognitive-behavioral therapy, combination pharmacologic and cognitive-behavioral therapy, or placebo, all treatment arms produced greater reduction in headache burden at 1- and 6-month follow-up compared with placebo [5]. Reduction in headache symptoms was greater when cognitive-behavioral therapy was combined with pharmacotherapy, suggesting a distinct mechanism and role for this modality.

Implementation — Behavioral treatments can be applied in a clinic-based format with sessions involving one-to-one contact between the patient and a psychologist or counselor [6]. Alternative formats for delivery of behavioral self-management techniques include small-group therapy and home-based (minimal-contact) treatment [6].

While some individuals can gain expertise through self-learning via commercially available videos or internet-based programs, current evidence supports professional application. Referral to a community-based pain psychologist is advised if the practitioner does not have access to readily available behavioral therapy resources.

Tricyclic antidepressants — For patients with severe TTH symptoms that do not respond to nonpharmacologic therapies, we use or add tricyclic antidepressants. In addition, we use tricyclic antidepressants for initial pharmacologic therapy when patients are unwilling or unable to adhere to nonpharmacologic therapies. These medications have the best evidence of efficacy for TTH.

Tricyclic antidepressants are reuptake inhibitors of serotonin and noradrenaline, and these neurotransmitter interactions are the presumed mechanism of action for this class of drugs. Negative data regarding selective serotonin reuptake inhibitors (SSRIs) suggest that other potential mechanisms, including inhibition of norepinephrine reuptake and antagonism of N-methyl-D-aspartate (NMDA) receptors, may be more likely to mediate the analgesic effect of tricyclics [16]. Amitriptyline also reduces pericranial muscle tenderness, leading to peripheral antinociception and inhibition of central sensitization [17,18]. Patients should be informed that amitriptyline is an antidepressant agent but has an independent action on pain [2]. The beneficial effect for TTH is not related to the presence of depression [19].

Amitriptyline — We suggest amitriptyline rather than other medications for initial pharmacologic management of most patients with frequent episodic TTH or chronic TTH, in agreement with guidelines from the European Federation of Neurological Societies on the treatment of TTH [2]. Other tricyclic agents may be used for those with an intolerance or contraindication to amitriptyline. We switch to alternative medications for patients who do not respond or have a contraindication to tricyclic antidepressants.

●Dosing – We start amitriptyline orally at 10 to 12.5 mg nightly and increase the dose in 10 to 12.5 mg steps every two to three weeks as tolerated and as needed until there is improvement in headache or until a maximum dose of 100 to 125 mg nightly is reached. To best assess responsiveness, amitriptyline should be titrated to a therapeutic dose of 75 mg, if tolerated [8,19].

An alternative titration schedule is to initiate amitriptyline at 25 mg each night and increase the dose in 25 mg increments each week. However, in the author’s clinical experience, such a regimen may reduce adherence by increasing the rate of adverse effects.

●Adverse effects – Tricyclic antidepressant medications may cause several adverse effects depending on specific agent and dose. These include cardiac conduction abnormalities, drowsiness, orthostatic hypotension, constipation, urinary retention, tremor, and blurred vision. (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects", section on 'Side effects'.)

●Managing risk of cardiac conduction abnormalities – Tricyclic medications are associated with an increased risk of cardiac conduction abnormalities and arrhythmias. Before initiating treatment with any of the cyclic antidepressants, patients should be screened for cardiac conduction system disease, which precludes the use of these medications. All patients should have baseline laboratory testing including serum potassium to exclude (or treat) hypokalemia. In addition, we suggest that patients 40 years and older have a baseline electrocardiogram (ECG) prior to starting a tricyclic medication. Patients younger than age 40 years who have history or symptoms of cardiac disease should also have a baseline ECG. Tricyclics are typically contraindicated when the corrected QT interval is >500 milliseconds.

Patients who have a normal ECG before starting a tricyclic antidepressant do not need additional ECG monitoring while on the antidepressant, unless symptoms arise suggestive of cardiac toxicity. (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects", section on 'Cardiac evaluation'.)

●Efficacy – Supporting evidence for the use of tricyclics in TTH comes from a 2017 meta-analysis of five placebo-controlled trials that included 387 patients, most assessing amitriptyline [20]. The reduction in monthly headache frequency (from a mean monthly baseline of 20.6) was greater in patients assigned to amitriptyline than those assigned to placebo as early as four-week follow-up (mean difference -4.8 headaches/month) and persisting up to 24-week follow-up (-5.0 headaches/month). Tricyclics were also associated with a reduction in use of analgesic medications. However, amitriptyline did not reduce headache severity or duration and treatment did not increase the proportion of patient with a ≥50 percent improvement. The paucity of trial data on other tricyclics limits the assessment of their comparative efficacy.

Alternative tricyclic agents — Nortriptyline and protriptyline can be used as alternative tricyclics if amitriptyline is poorly tolerated due to excess sedation or unwanted weight gain.

●Nortriptyline formulated in capsules and started at 10 mg nightly. It can be titrated as needed and tolerated increasing in 10 or 25 mg increments on a weekly basis up to a typical maximum dose of 100 mg. Nortriptyline is mildly sedating, but sedative effects and risk of weight gain are lower than with amitriptyline.

●Protriptyline is started at 5 mg each morning and increased in 5 mg increments every week with a target dose of 20 mg each morning. Some patients may need doses up to 60 mg each morning. Unlike other tricyclics, protriptyline can be stimulating and may cause weight loss [21]. Protriptyline should be used cautiously in patients who have anxiety and panic disorders.

Baseline testing and monitoring is warranted for patients taking nortriptyline or protriptyline to manage the risk of cardiac conduction abnormalities associated with tricyclic antidepressants. (See 'Amitriptyline' above.)

Combination tricyclic and behavioral therapy — Although data are limited, combination behavioral plus tricyclic therapy may produce a more rapid effect than either modality alone. Behavioral therapy and tricyclic therapy appear to have equivalent individual modest effectiveness for the treatment of chronic TTH, while tricyclic therapy achieves benefit more rapidly.

In a clinical trial of 203 patients with chronic TTH, the proportion of patients who achieved a clinically significant (ie, ≥50 percent) reduction in baseline headache index scores at one-month follow-up was higher in the group assigned to stress management plus tricyclic therapy than groups assigned to tricyclic therapy alone, stress management therapy alone, or placebo (64 versus 38, 35, and 29 percent, respectively) [5]. At six months, reductions in baseline headache index were similar for all three active treatments. The overall magnitude of benefit was modest; each active treatment reduced the number of days a month with a headache of moderate or greater severity by half (from approximately 14 to 7 days).

Alternative medications — For patients with TTH who do not respond or have a contraindication to tricyclic antidepressants, we switch to an alternative agent from a different class. We add an alternative agent for patients with a partial response to tricyclics.

Limited data from small randomized controlled trials suggest that some alpha-adrenergic antagonists, serotonin-norepinephrine reuptake inhibitors, and antiseizure medications may be effective for the treatment of patients with chronic TTH.

●Mirtazapine — Mirtazapine is given at 15 mg once daily at bedtime and may be increased as needed and tolerated after one week to 30 mg. Mirtazapine may cause drowsiness, weight gain, and constipation.

In an eight-week trial involving 24 patients with chronic TTH, including subjects not responsive to amitriptyline, mirtazapine (15 to 30 mg daily) treatment was associated with a modest reduction in headache burden [22]. In addition, mirtazapine treatment also associated with reductions in headache intensity, duration, and frequency. More patients treated with mirtazapine had sedation, dizziness, and weight gain than did patients receiving placebo, but the difference was not statistically significant. However, weight gain is a known side effect of mirtazapine, and the short duration of the trial may explain why the relationship did not achieve statistical significance.

●Venlafaxine — Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used for depression that may also be effective for some patients with TTH. Venlafaxine is started at 37.5 mg daily and increased by 37.5 mg increments each week up to a maximum of 150 mg daily. Common adverse effects with venlafaxine include nausea, dizziness, insomnia, weight loss, and diaphoresis.

In a 12-week trial involving 60 patients with TTH and more than five headaches a month at entry, treatment with extended-release venlafaxine (150 mg daily) was associated with fewer headache days, the primary outcome measure, compared with placebo (45 percent reduction versus 16 percent increase) [23]. Adverse events, mainly gastrointestinal symptoms, were more frequent in the venlafaxine group.

●Gabapentin — Gabapentin is typically used at an effective dose range from 900 to 2400 mg/day in three divided doses but is started at 300 mg daily and increased by 300 mg every three to seven days as tolerated to reduce risk of sedation, dizziness, and ataxia. Gabapentin may also cause respiratory depression and should be used with caution in patients with respiratory disorders.

Direct evidence of benefit for gabapentin in TTH prevention is lacking, but one randomized trial evaluated this drug in 95 patients with chronic daily headache, including 25 patients with TTH and 58 with a combination of TTH and migraine [24]. Treatment with gabapentin (2400 mg daily) was associated with an improvement in headache-free days compared with placebo. The strength of this finding is limited by methodologic problems with the study, including failure to use an intention-to-treat analysis.

●Topiramate — Topiramate is typically started at 25 mg once daily and increased weekly as needed and tolerated by 25 to 50 mg up to a typical maximum dose of 100 mg twice daily. Common adverse effects include sedation, paresthesias, weight loss, and depression.

An open-label study of topiramate (initially 25 mg daily, then increased to 100 mg daily) in 51 patients with TTH reported a significant decline in headache frequency after three months of treatment [25]. Further evidence from randomized clinical trials is needed to clarify whether topiramate has a role in TTH prevention.

●Tizanidine — Tizanidine is a muscle relaxant and antispasticity agent. The usual starting dose of tizanidine is 2 mg daily and may be increased in 2 mg increments every three to seven days up to a typical maximum effective dose of 18 mg daily. Tizanidine may cause dry mouth, dizziness, and sedation.

There are limited and conflicting data regarding the effectiveness of tizanidine for the prophylaxis of TTH [26-29]. An early clinical trial of 37 females with chronic TTH found that tizanidine (6 to 18 mg daily) was more effective than placebo [26]. However, a larger trial of 185 patients with chronic TTH showed that tizanidine (6 or 12 mg modified release daily) was without benefit compared with placebo [27].

An open-label trial of 18 subjects with chronic TTH reported that combined treatment with tizanidine (4 mg daily for three weeks) and amitriptyline (20 mg daily for three months) led to faster reduction in headache frequency, intensity, and duration than amitriptyline alone [30]. The small size and open-label nature of this trial precludes definitive conclusions.

Available evidence suggests that SSRIs are not effective for the treatment of TTH in patients without depression [7]. This conclusion is supported by a meta-analysis published in 2015, which found that SSRIs did not find benefit for patients with TTH [31].

OTHER TREATMENT OPTIONS — 

Some physical (nonbehavioral) nonpharmacologic and interventional therapies may also be used for preventive treatment of TTH. These options include physical therapies, acupuncture, local injections, and neuromodulation.

Physical therapies — The benefit of physical therapy for TTH is unproven, though some studies suggest promise [32]. For patients with frequent episodic TTH and chronic TTH who do not tolerate or desire initial nonpharmacologic or pharmacologic treatments, we typically refer for physical therapy for treatment that includes craniocervical exercises. These treatments are associated with a low risk of serious side effects [32,33].

However, multiple physical therapy methods, alone or in combination, have been used to treat TTH [32]. Common modalities with some evidence of efficacy include:

●Physiotherapy with exercises targeting neck/shoulder muscle tenderness

●Therapeutic heat or cold

●Massage

●Postural correction

●Spinal manipulation, traction, and/or inactivation of muscle trigger points

There are few high-quality randomized trials evaluating the effectiveness of physical therapy for TTH prevention. A 2014 systematic review identified six randomized controlled trials evaluating manual therapies that involved 249 subjects with TTH (mostly chronic TTH) [34]. One trial evaluated massage, and five evaluated physiotherapy. Only two studies avoided cointervention, leading to potential problems with bias and interpretation of the results. In one of the larger trials included in the systematic review, 81 patients with TTH were randomly assigned to a program of craniocervical strength exercises combined with standard physical therapy (massage, oscillation techniques, postural correction) or to physical therapy alone [35]. Combined craniocervical training plus physical therapy was associated with a trend toward reduction in headache frequency compared with physical therapy at six weeks, but a significant benefit in the reduction in headache frequency was found at six months (1.95 fewer headaches per week, 95% CI 1.14-2.76). In addition, headache intensity and duration at six months were significantly reduced with combined treatment.

Several manual therapies (eg, spine mobilization or manipulation, low-load stabilization exercises, soft tissue pressure release, and postural correction) were assessed in a meta-analysis that identified five small randomized controlled trials [36]. In pooled data, manual therapies were associated with reduced headache frequency compared with pharmacologic therapies at two weeks; this effect was not sustained at longer time points. Major limitations included lack of blinding (only one of the trials blinded assessors, and none blinded therapists or subjects) and heterogeneity of the treatments.

Osteopathic manipulative therapy uses a variety of techniques including massage, low-velocity manipulations, and postural correction, depending on body area. Proposed methods for inactivating muscle trigger points include dry needling, ultrasound, laser, electrotherapy, and manual therapies [37,38]. However, the best technique is not yet defined, nor is it known if there is any particular subgroup of patients who are more likely to respond to these methods. In a single-blind randomized controlled trial pilot study of 40 subjects with frequent episodic TTH not on prophylactic regimens that randomly assigned patients to corrective osteopathic manipulative therapy or sham therapy, active treatment led to an improvement in headache frequency at one and three months with an absolute reduction in headache frequency of 33 percent at three months [39].

Strength training was associated with a moderate improvement in pain intensity in a meta-analysis of three small trials, but the certainty of these results was very low due to small number of patients assessed, risk of bias, and varied protocols used [40].

Acupuncture — Some evidence suggests acupuncture may have modest benefits for patients with TTH [41]. In one trial of 270 patients with chronic TTH, acupuncture treatment was associated with fewer days with headache compared with control patients assigned to wait list [42]. However, acupuncture intervention may not provide benefit over minimal (sham) acupuncture, suggesting that treatment with any acupuncture technique may have measurable therapeutic effects [43].

A meta-analysis updated in 2016 identified seven randomized trials with sham controls [44]. The proportion of patients who achieved a ≥50 percent reduction of headache frequency, the primary outcome, was greater with acupuncture; however, the effect size was small (51 versus 43 percent), and the quality of the evidence was rated as moderate.

Although of limited benefit for the prevention of TTH, acupuncture appears to be safe and may provide benefit for some patients who do not tolerate or desire other nonpharmacologic treatments. (See "Overview of the clinical uses of acupuncture".)

Local injection treatments

●Trigger point injections – Limited data from small randomized controlled trials suggest that trigger point lidocaine injections may reduce headache frequency and, thereby, total acute medication use for patients with frequent episodic or chronic TTH [45,46]. The role of trigger point injections in TTH remains uncertain and requires more research.

●Botulinum toxin injections – In a 2023 meta-analysis, 11 placebo-controlled trials evaluated onabotulinumtoxinA (botulinum toxin type A) for patients with chronic TTH [47]. Botulinum toxin injections led to a small reduction in the frequency, duration, and intensity of headaches, as well as lower use of acute pain medications. However, the absolute response rate with botulinum toxin injections was 12 percent, suggesting benefit of this therapy for unselected patients with TTH may only benefit a minority of patients. The quality of evidence was low to moderate. Given these data, the benefit of botulinum toxin injections for the preventive treatment of TTH is uncertain.

Neuromodulation — Multiple noninvasive neuromodulation techniques have been used for TTH with limited data showing some benefit for electrical therapies such as transcutaneous electrical nerve stimulation (TENS), electromagnetic therapy, ultrasound, and laser [2,33]. Additional data are needed to better assess the benefit of these techniques and to identify patients for these options.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Migraine and other primary headache disorders".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (See "Patient education: Headache treatment in adults (Beyond the Basics)".)

SUMMARY AND RECOMMENDATIONS

●Indications for treatment – Prophylactic headache treatment is indicated if the headaches are frequent, long lasting, or are disabling. This includes patients with TTH and the following features (see 'Indications for preventive treatment' above):

•frequency >2 headache days each week,

•duration >4 hours, or poorly responsive to acute therapies, OR

•severity that impairs functioning (disabling).

●Treatment selection – TTH treatment should be individualized. We typically start with nonpharmacologic therapies such as biofeedback and relaxation therapy, stress and headache trigger management, or other specific interventions. For patients with severe symptoms and those who prefer pharmacotherapy, we use or add preventive medications for TTH (algorithm 1). (See 'Our approach' above.)

●Initial therapy

•Behavioral therapy – For most patients with TTH, we suggest initial treatment with a behavioral therapy (Grade 2C). Biofeedback combined with relaxation therapy has the best evidence of efficacy; alternatives include biofeedback or relaxation therapy alone, self-management, and cognitive-behavioral therapy. The goal of behavioral treatments is to prevent headaches by identifying and defusing headache triggers. Behavioral therapies can target specific headache triggers, and several modalities have been shown to modestly reduce headache burden in multiple studies. (See 'Behavioral therapies' above.)

•Tricyclic antidepressants – For patients with frequent episodic TTH or chronic TTH, we suggest tricyclic therapy with amitriptyline, rather than other agents for initial pharmacotherapy (Grade 2C). The effectiveness of amitriptyline, while modest, has been established in multiple trials. We start amitriptyline at 10 to 12.5 mg nightly and increase the dose in 10 to 12.5 mg steps every two to three weeks as tolerated and as needed until there is improvement in headache up to a maximum dose of 100 to 125 mg nightly. (See 'Amitriptyline' above.)

Benefit is often first noted after four to six weeks of therapy. Once an effective regimen is identified, we maintain therapy for at least three to six months. Thereafter, a slow taper can be attempted. The regimen can be resumed if symptoms relapse. (See 'Pharmacologic treatment principles' above.)

•Alternative oral medications – For patients with TTH who do not respond or have a contraindication to tricyclic antidepressants, we switch to an alternative agent from a different class. We add an alternative agent for patients with a partial response to tricyclics. Oral options include (see 'Alternative medications' above):

-Antidepressants (eg, mirtazapine or venlafaxine)

-Antiseizure medications (eg, gabapentin or topiramate)

-Muscle relaxants (eg, tizanidine)

●Other treatment options – Physical (nonbehavioral) nonpharmacologic and interventional therapies may also be used for preventive treatment of TTH. These options include physical therapies, acupuncture, local injections, and neuromodulation. (See 'Other treatment options' above.)