{"paper_id":"0b14c32f-0a4c-4cb9-9b5f-5ea584fbb671","body_text":"Medication overuse headache (MOH) is a secondary form of headache that \nsuperimposes a chronic primary headache [ 1 ]. Specifically, MOH is diagnosed in \npatients experiencing ≥15 headache days per month and using an excessive \nnumber of symptomatic headache medications for more than 3 months [ 2 ]. Far from \nbeing a rare condition, MOH accounts for approximately half of all visits to \nspecialized headache centers and affects over 70% of all patients with chronic \nheadaches [ 3 ]. However, MOH prevalence in the general population is significantly \nlower, ranging from 0.5% to 7.2% across different countries [ 4 ]. This \ndiscrepancy reinforces the idea that MOH and the overuse of acute medication \nrepresent two clinical hallmarks of a more disabling headache, heralding poor \nresponse to treatments [ 5 ]. MOH is directly related to both the type and quantity \nof the overused acute medications. The threshold for “overuse” is defined as \n≥15 days per month for nonsteroidal anti-inflammatory drugs (NSAIDs), and \n≥10 days per month for other classes of medications including triptans, \ncombination analgesics, opioids, and ergot derivatives [ 4 ]. While it seems quite \nrobust that opioids and barbiturates have a higher chance of inducing MOH, the \nrole of triptans in causing MOH is still debated, although their threshold \nremains precautionary lower than NSAIDs [ 6 ].\nBeyond the type of acute medication used, several additional risk factors are \nknown to influence the development of MOH. It most commonly occurs in patients \nwith migraine as the underlying headache disorder, followed by tension-type \nheadache (TTH), post-traumatic headache, and new daily persistent headache [ 7 ,  8 ]. In contrast, MOH development in patients with pure cluster headache remains \ncontroversial. Moreover, female sex, low education, economic disadvantage, and \nsmoking are all associated with a higher risk of MOH [ 9 ].\nAmong the modifiable risk factors, metabolic syndrome, obesity, and physical \ninactivity are strongly linked to MOH. Whereas the first two conditions are \ngenerally associated with chronic migraine (CM), physical inactivity (defined as \n<3 hours of vigorous physical activity per week) is specifically associated \nwith the risk of MOH [ 10 ].\nMusculoskeletal pain and other co-existing painful conditions represent \nadditional risk factors for MOH. The relationship between multiple pain disorders \nis so closely intertwined that recently ten conditions ( i.e. , \nmusculoskeletal pain, temporomandibular disorder, fibromyalgia, irritable bowel \nsyndrome, vulvodynia, myalgic encephalomyelitis/chronic fatigue syndrome, \ninterstitial cystitis/painful bladder syndrome, endometriosis, and pelvic floor \npain) are now grouped under the term chronic overlapping pain conditions (COPCs) \n[ 10 ,  11 ].\nMoreover, psychiatric comorbidities are more prevalent in MOH. Most notably, \ndepression and anxiety have been consistently reported [ 12 ], and in MOH patients \nwith multiple therapeutic failures, also bipolar disorder is quite common [ 13 ]. \nFurthermore, MOH patients tend to show different personality traits compared with \npatients without MOH [ 14 ].\nThis result is also in line with new evidence showing that both childhood \nemotional and physical trauma are strong determinants of the future development \nof MOH. In particular, when childhood trauma is associated with the presence of \nalexithymia, the risk of developing a somatization disorder increases [ 15 ].\nThe possible overlap between patients with MOH and those with substance use \ndisorder remains controversial. However, a seminal neuroimaging study has shown \nthat the orbitofrontal cortex remains metabolically hypoactive even after \nwithdrawal therapy, whereas other brain regions previously affected by MOH return \nto a metabolic activity comparable to that of healthy controls [ 16 ].\nA recent study suggests that CM patients could be divided into two categories. \nOn one side, “pure” CM with less comorbidities and risk factors, who have a low \nrisk of developing MOH and who can, in general, experience transient medication \noveruse. On the other side, CM patients with multiple MOH risk factors, who are \nmore likely to develop MOH early in the course of migraine chronicity or to \nrelapse after withdrawal. In “pure” CM patients without prior history of MOH, \nthe annual incidence of MOH is approximately 17% per year, increasing to 33% in \nthose unresponsive to preventive treatments [ 17 ]. However, in patients with a \nprevious history of MOH, relapse rates increase up to 66–78% in the following \nyears [ 18 ,  19 ].\nTaken together, these data explain why the management of MOH has always \nrepresented a complex issue in the headache field. For many years, it has been \ndebated whether a standardized detoxification strategy is necessary to interrupt \nmedication overuse (MO) or whether effective headache prevention alone may be \nsufficient to avoid the development of MOH. This debate has become particularly \nrelevant in recent years with the introduction of new preventive medications, \nwhich have reinforced the idea of avoiding formal detoxification [ 20 ].\nWhile transient MO without progression to MOH can also occur in episodic \nmigraine (EM) patients [ 21 ], the development of MOH is typically accompanied by a \nprogressive increase in headache frequency, and by specific modifications of \nneuronal excitability at peripheral and central level of the nervous system. \nNotably, emerging evidence suggests that some of these modifications may be \npartially reversible in the presence of protective factors [ 17 ].\nAmong the mechanisms implicated, central sensitization is probably one of the \nmost important processes involved in MOH, as demonstrated by neurophysiological \nstudies in humans [ 22 ] and mice models [ 23 ,  24 ]. In humans, functional magnetic \nresonance imaging (fMRI) studies reported findings consistent with central \nsensitization, showing stronger pain-induced responses within the pain \nneuromatrix and in several brain regions, including the motor cortex, superior \ntemporal sulcus, premotor cortex, supplementary motor area, lingual gyrus, \ndorsomedial prefrontal cortex, anterior cingulate cortex, and primary \nsomatosensory cortex [ 25 ]. Compared with CM without MOH, those with comorbid MOH \nexhibit more severe functional and structural alterations [ 25 ,  26 ]. \nEncouragingly, these alterations seem to revert following recovery from MOH [ 27 ].\nDue to the complexity of MOH presentations, a multidisciplinary, integrated \napproach is increasingly viewed as a valuable strategy for management [ 28 ]. While \nnot all MOH patients may require such an approach, those with high relapse risk, \nprevious treatment failures, severe clinical burden, or psychiatric comorbidities \nare likely to benefit from a combined therapy [ 28 ]. To date, however, several \nelements of this approach remain insufficiently defined, including the specific \ncomponents of the intervention, involved specialties, and optimal composition of \nthe multidisciplinary team. In most studies, teams comprise neurologists, \npsychologists, physiotherapists, and headache nurses, although some evidence also \nsupports the inclusion of occupational therapists, health educators, and aerobic \nexercise trainers [ 29 ]. Another key consideration is the setting in which the \nintervention is delivered. Current evidence suggests that outpatient or \nday-hospital models offer comparable clinical effectiveness [ 30 ], while also \nproviding greater practicality and cost-efficiency [ 31 ]. An important exception \nto an outpatient setting arises when patients present significant systemic \ncomorbidities, require withdrawal from drugs such as opioids or barbiturates, or \nhave previously failed outpatient detoxification attempts [ 32 ]. In addition, with \nregard to the optimal duration of intervention, no consensus has been reached, \nwith available evidence ranging from 180 minutes to 96 hours [ 28 ].\nThe major advantage of non-pharmacological interventions lies in their \napplicability even in presence of multiple comorbidities. In fact, they may be \nespecially beneficial for patients with conditions such as anxiety, depression, \nasthma, obesity, or metabolic syndrome. These comorbidities not only predict \npoorer outcomes [ 33 ], but represent  per se  an impediment to use some \npharmacological preventive therapies—either due to contraindications or \ntolerability issues. For instance, beta-blockers are contraindicated in asthma, \nvalproate is discouraged in obesity, and topiramate should be avoided in patients \nwith suicide ideation.\nDespite growing interest, multidisciplinary approaches for MOH have not been \nsystematically compared to other strategies of MOH management, with the exception \nof a few studies [ 31 ,  34 ]. Nonetheless, observational studies found responder \nrates above 50%, ranging from 43% to 63% [ 29 ,  35 ,  36 ]. An open-label study \ncompared gradual detoxification to abrupt withdrawal combined with \nmultidisciplinary education. Both groups achieved a ≥80% success rate, \nhowever the multidisciplinary education group required fewer staff resources and \nneeded fewer prophylactic drugs after detoxification [ 34 ]. A visual \nrepresentation of several non-pharmacological interventions used in the \nmultidisciplinary management of MOH is provided in Fig.  1 , while  Table 1  (Ref. \n[ 34 ,  35 ,  37 ,  38 ,  39 ,  40 ,  41 ,  42 ,  43 ,  44 ,  45 ,  46 ,  47 ]) summarizes and compares the main characteristics of the \nincluded studies.\nVisual representation of several non-pharmacological approaches \nfor the multidisciplinary management of MOH. Created in BioRender. Balordi M. \n(2026)  https://BioRender.com/tm0uc2b . EMDR: \neye movement desensitization and reprocessing; PNE: pain neuroscience education.\nCited articles for each non-pharmacological intervention.\nMOH: medication overuse headache; RCT: randomized controlled trial; MIDAS: \nMigraine Disability Assessment Score Questionnaire; QoL: Quality of Life; MHD: \nmonth headache days.\n\nThe present article is a narrative review of the literature on \nnon-pharmacological and multidisciplinary interventions for the management of \nMOH. A narrative approach was selected instead of a systematic review or \nmeta-analysis because of the substantial heterogeneity of non-pharmacological \ntreatments and the wide variability of interventions in terms of intensity, \nnumber, and frequency of sessions. In addition, many non-pharmacological trials \non CM or chronic TTH, often exploratory in nature, do not clearly report whether \npatients with MOH were included or excluded. Given that a large proportion of \npatients with CM also meet criteria for MOH, non-pharmacological studies on CM \nwere included unless it was explicitly stated that only patients with CM were \nenrolled or that other primary headache disorders were excluded.\nThe research team conducted a structured non-systematic literature search \nthrough PubMed/MEDLINE and Google Scholar databases. The search was conducted in \nJuly 2024 and updated in May 2025. Keywords included combinations of terms such \nas “medication overuse headache”, “MOH”, “non-pharmacological treatment”, \n“multidisciplinary treatment”, “patient education”, “psychotherapy”, \n“physical therapy”, “neuromodulation”, and “complementary medicine”.\nWe included peer-reviewed articles in English, published from 2000 up to May \n2025, including selected earlier works of historical or clinical relevance. \nEligible studies involved adult populations and addressed non-pharmacological or \nmultidisciplinary interventions relevant to MOH. The research excluded studies \nfocusing exclusively on pharmacological approaches, pediatric populations, case \nreports, and non-peer-reviewed publications.\nFinally, findings were synthesized thematically and presented according to \nintervention type. Given the heterogeneity of methodologies, no formal quality \nassessment or quantitative synthesis was conducted.\n\nTo date, the mainstay of MOH management remains the discontinuation of the \noverused medication through withdrawal therapy that should be implemented even \nwhen other therapeutic approaches are not possible, although recent evidence \nshowed that combing it with preventive therapy provides a better outcome \n[ 48 ,  49 ,  50 ]. This may indeed be complemented by bridging analgesics and/or \nprophylactic agents, if deemed appropriate. Nevertheless, further research is \nwarranted to optimize this strategy.\nWithdrawal protocols vary also depending on the type of overused drug. Inpatient \nmanagement is recommended for patients overusing opioids, benzodiazepines, or \nbarbiturates, while outpatient detoxification is generally considered sufficient \nfor other medication classes [ 51 ]. The choice between abrupt withdrawal and \ngradual tapering remains a topic of debate [ 52 ]. Gradual tapering is advised for \nbarbiturates and opioids to mitigate withdrawal symptoms, whereas for other \ndrugs, abrupt cessation appears more effective than gradual reduction [ 3 ]. \nImportantly, evidence suggests that structured detoxification program, when \npaired with close follow-up, is highly effective [ 34 ]. Regardless of the modality \nof medication interruption, sustained avoidance of medication overuse is \nassociated with improved medium- and long-term outcomes [ 53 ,  54 ,  55 ].\nBridging therapy with analgesics could be primarily offered to patients in the \noutpatient setting, to increase patient compliance and as alternative to down \ntapering alone. Long-lasting analgesics ( e.g. , naproxen) are the \ndrug-of-choice in bridging therapy for a couple of weeks. The duration of \nbridging therapy is based on the duration of withdrawal symptoms, lasting for up \nto 10 days for NSAIDs, around 4 days for triptans, and about 7 days for ergot \nderivatives [ 56 ]. During hospitalization or day-hospital withdrawal [ 57 ], \nintravenous administration of acetylsalicylic acid [ 58 ], or corticosteroids [ 59 ,  60 ] may be used alone or in combination with supportive measures such as \nhydration, antiemetics, clonidine, or benzodiazepines. Notably, corticosteroids \nappear to be the most controversial choice among the possible rescue medications \n[ 61 ].\nPatient education represents a crucial component in the management of MOH [ 54 ]. \nExplaining, in accessible terms, what MOH is and how it develops enables patients \nto adopt appropriate behaviors to discontinue MO, while at the same time \nmaintaining adherence to prescribed treatments. MOH education primarily aims to \ninform patients about the role of acute medications in perpetuating headaches, \nand to emphasize the importance of interrupting overuse in order to revert \nchronicity and prevent recurrence. In the past, some seminal studies have shown \nthat, in patients with uncomplicated MOH, this “advice-only” approach can \nachieve detoxification rates comparable to those of more intensive inpatient or \noutpatient medication-based programs [ 50 ,  52 ]. However, this net benefit cannot \nbe generalized to patients with complicated MOH [ 49 ].\nAnother critical issue in the management of MOH concerns the timing of \npreventive therapy initiation—whether it should be started concomitantly with \nwithdrawal or delayed until after a period of withdrawal alone, typically lasting \nthree months [ 34 ]. This question remains unresolved and is generally addressed on \na case-by-case basis, taking into account factors such as previous failed \nwithdrawal attempts, headache burden, and the presence of comorbidities, \nincluding psychiatric conditions [ 52 ]. Recent evidence suggests that preventive \ntherapy may be more effective than withdrawal alone, particularly following the \nintroduction of new migraine-specific preventive agents. However, the actual role \nand magnitude of the effect of these medications in MOH management remain under \ninvestigation [ 62 ,  63 ]. Reported rates of MOH resolution with preventive \ntreatments ranges widely, from 29% to 88% of patients [ 64 ]. While some authors \npropose that these new therapies may reduce the need for, or even allow the \nomission of, formal withdrawal, others support the opposite approach [ 20 ,  65 ]. \nOne potential confounding factor in this debate is drug dosage, which may \ndifferentially influence outcomes, as demonstrated for monoclonal antibodies \nadministered at different doses [ 66 ]. Further studies are needed to better \nclarify the impact of calcitonin gene-related peptide (CGRP)-targeting monoclonal \nantibodies in MOH management.\nDue to the close relationship between the development of MOH and emotional \ndistress, dysfunctional thoughts, psychiatric and psychological comorbidities \n[ 67 ], the pairing of pharmacological treatments with psychological support could \nhelp patients with coping and prevent MOH relapses [ 68 ]. The European Academy of \nNeurology endorsed Short-term Psychodynamic Psychotherapy (STPP) and mindfulness \nas potentially helpful in MOH management [ 68 ].\nSTPP is a Freudian-inspired psychotherapy approach that considers migraine \nheadache as a psychosomatic disorder. It attributes the condition to the \npatient’s previous traumatic experiences, suffering, and aspirations, which are \nconsidered in terms of intra-psychic conflicts [ 69 ]. Mentalization—the ability \nto process emotional conflicts and express them through words—emerges as a key \nprotective factor. This ability is shaped by a combination of personal and \nenvironmental factors, with higher levels of mentalization linked to more \nsophisticated and effective emotional regulation. In turn, this is associated \nwith a lower risk of psychosomatic symptoms and, consequently, a reduced \nlikelihood of migraine chronification. In a recent study, we found that in \naccordance with the STPP model, CM and MOH patients tend to express low or \nintermediate levels of mentalization, which may favor the development of chronic \nheadache symptoms. Therapeutic STPP aims at helping the patient to elaborate past \nconflicts and the associated emotional burden, in order to get a resolution of \nboth intra-psychic conflicts and consequently headache symptoms [ 70 ].\nMindfulness, defined as a focused, non-judgmental awareness of the present \nmoment, has been investigated in migraine, but to date its real effectiveness is \nunder investigation since recent systematic reviews have not established a clear \nbenefit [ 71 ]. However, recent phase III trials involving 177 patients, reported \nthat mindfulness, when added to standard care ( i.e. , withdrawal, \neducation, and prophylaxis), led to greater improvements in terms of headache \nfrequency, medication intake and quality of life (QoL) [ 72 ].\n\nBesides the therapies and approaches discussed above, several emerging \nnon-pharmacological interventions may hold potential in the field of migraine \nfield and, in particular, in the management of MOH, given the complex clinical \npresentation of these patients. However, most of these interventions have been \ninvestigated only in recent years, with preliminary findings that are promising, \nbut limited in number and often lacking replication. Moreover, the available \nevidence largely derives from studies conducted in the broader migraine \npopulation, with only a few investigations specifically targeting patients with \nMOH. As a result, the overall level of evidence supporting their efficacy in MOH \nremains low. Nevertheless, owing to their favorable safety profiles, some of \nthese approaches warrant further investigation in future studies. In the \nfollowing section, a brief outline is provided regarding non-pharmacological \ninterventions that may represent potential adjuncts to standard therapy in the \nmanagement of MOH.\nAmong the most commonly used psychotherapeutic approaches, cognitive-behavioral \npsychotherapy (CBT) is one the most extensively investigated in the field of \nmigraine, particularly in combination with other behavioral techniques. However, \nits specific role in the management of MOH is less clearly defined than for other \nheadache conditions [ 73 ]. CBT aims to help patients process pain-related negative \nemotions and dysfunctional thoughts, identify triggers, modify maladaptive \nhabits, and ultimately develop preventive coping strategies [ 74 ]. In patients \nwith MOH, CBT combined with other behavioral interventions has been evaluated in \na double-blind RCT, delivered by trained professionals during the withdrawal \nphase, and was associated with MOH resolution in approximately 7% more patients \ncompared with standard therapy alone [ 75 ].\nAnother possible psychotherapeutic approach that may be of interest in the \nmanagement of MOH is Eye Movement Desensitization and Reprocessing (EMDR). This \ntechnique is typically proposed as an adjunctive intervention within a \npsychotherapeutic framework, primarily for the treatment of post-traumatic stress \ndisorder [ 76 ]. EMDR involves bilateral visual, auditory, and tactile stimulation \naimed at facilitating the desensitization and reprocessing of traumatic memories. \nTwo studies have investigated the use of EMDR in patients with migraine, without \ndetailed characterization of patient profiles (see review [ 77 ]). The two studies \ndiffered in the modality of EMDR delivery, namely visual-only versus combined \nvisual–tactile stimulation. The first study focused on headache-related \ntraumatic experiences and reported that three months of EMDR were associated with \nreductions in both headache days and acute medication use, with sustained \nbenefits at follow-up [ 77 ]. The second study, a larger RCT, showed that EMDR used \nas an add-on to standard preventive therapy led to faster and more pronounced \npain relief [ 77 ].\nGiven the central role of patient education in the management of MOH, one might \nspeculate that a more structured and in-depth educational approach may be more \neffective than brief or purely informational interventions, such as providing \nshort counselling or written materials. Pain Neuroscience Education (PNE) may \nrepresent a valuable resource for implementation in patients with MOH. While \ntraditional biomedical education primarily focuses on tissue damage as the cause \nof pain [ 78 ], PNE aims to enhance patients’ understanding of pain neurophysiology \nand neurobiology, pain representation, and the meaning of pain. PNE is considered \na behavioral intervention that primarily targets coping strategies, which are \noften dysfunctional in patients with migraine and MOH [ 79 ,  80 ,  81 ]. Indeed, PNE has \nbeen shown to improve coping strategies and scores on the Central Sensitization \nInventory, Pain Catastrophizing Scale, and Tampa Scale of Kinesiophobia, even in \nthe absence of a direct effect on pain intensity [ 82 ].\nRecently PNE has been implemented with promising results in several chronic pain \nconditions, including cancer-related pain [ 83 ,  84 ,  85 ,  86 ]. However, for other chronic \npain entities, including fibromyalgia and headache in general, the evidence \nremains limited [ 87 ,  88 ,  89 ]. Recent reviews focusing on PNE in migraine have \nreported moderate to strong evidence of effectiveness, although uncertainties \nremain regarding optimal implementation parameters, including delivery modalities \nand the number of sessions required [ 90 ,  91 ]. At present, only a limited number \nof trials specifically targeting MOH are available. However, several studies in \npatients with CM, with and without MOH, are currently ongoing [ 92 ,  93 ]. Although \nthe existing literature does not yet support the routine application of PNE in \nthe management of MOH, it is noteworthy that the benefits of PNE appear to be \nenhanced when it is combined with other non-pharmacological interventions, \nyielding better outcomes than single intervention alone ( e.g. , physical \ntherapy) [ 94 ]. Overall, these findings may suggest that PNE could be worthy of \nfurther investigation in future MOH-focused studies.\nPhysiotherapy (PT) offers a broad spectrum of non-pharmacological interventions \nfor patients with migraine and MOH, including, among others, exercise programs, \nmanual therapy (MT), and dry needling (DN) [ 95 ]. Unfortunately, PT has only \nrecently been studied in the context of MOH with a single study by Trager \n et al . [ 96 ]. This study analyzed data from the USTriNetX network \n(covering over 124 million individuals) and found that patients who received MT \nwere less likely to develop MOH over the following 2-years, compared with those \nwho did not receive MT. The main rationale for PT in migraine, and MOH in \nparticular, lies in its ability to address musculoskeletal disorders \n( e.g. , neck pain) contributing to headache symptoms [ 95 ,  97 ]. PT \ninterventions in migraine may also include postural rehabilitation, balance \ntraining, and vestibular exercises, while encouraging active patient engagement \nand promoting lifestyle modifications [ 98 ]. Although the overall quality of \nevidence is still low, a recent meta-analysis showed that specific combinations \nof MT, exercise, and electrical stimulation can be effective in treating TTH \n[ 99 ]. In migraine, more complex PT strategies—such as occipital transcutaneous \nelectrical stimulation, acupressure, osteopathic MT, soft tissue mobilization, \nfacial proprioceptive neuromuscular facilitation, and aerobic exercise—have \nalso demonstrated some efficacy [ 95 ].\nFor chronic headaches, MT hands-on techniques ( e.g. , massage therapy, \njoint mobilization and spinal manipulation) could be valuable adjunctive \ntreatments [ 100 ]. Both soft tissue and articulatory MT have shown benefits in \nmigraines [ 101 ]. In particular, spinal manipulative therapy has been shown to \nsignificantly reduce headache frequency and intensity in chronic headache, with \neffects comparable to those of propranolol, topiramate, and amitriptyline [ 100 ]. \nHowever, uncertainties remain regarding standardized techniques to be used, the \noptimal number of sessions, and the appropriate duration of treatment.\nAerobic exercise regimens are also included in the physiotherapeutic \narmamentarium for migraine management [ 98 ]. Although in some cases physical \nactivity may trigger migraine attacks or exacerbate chronic pain, regular \nexercise appears to reduce both migraine frequency and pain perception over time \n[ 102 ,  103 ]. Clinical guidelines from the French, Danish, and American Headache \nSocieties support the inclusion of exercise as part of migraine management \n[ 104 ,  105 ,  106 ]. Accordingly, aerobic exercise and physical activity combined with \nhealthy lifestyle habits are classified as grade B recommendations for migraine \nmanagement [ 107 ]. In particular, strength training has been identified as the \nmost effective exercise modality for both CM and chronic TTH [ 108 ,  109 ]. \nMoreover, both high- and moderate-intensity aerobic exercise have shown efficacy \ncomparable to that of topiramate and amitriptyline in migraine management [ 110 ]. \nNevertheless, as in the case of MT, the application of exercise-based therapy \nlacks standardization, and further research is required to define optimal \nprotocols and to account for variables such as patient preferences, fitness \nlevels, and psychological factors [ 111 ].\nDry needling (DN) is a puncture technique based on inserting needles into \npainful areas, such as myofascial trigger points, sites whose stimulation is able \nto elicit local and referred pain [ 112 ,  113 ]. However, evidence on the efficacy \nof DN for headache remains very limited, due to heterogeneous headache types or \nlack of superiority over controls.\nNon-invasive neuromodulation has been investigated over the past decade in the \ncontext of migraine and CM. The rationale for its use lies in the potential to \nreverse maladaptive neuroplastic changes underlying central sensitization and the \nchronification process [ 114 ]. However, with the exception of single pulse \ntranscranic magnetic stimulation (sTMS) and peripheral transcutaneous electrical \nnerve stimulation (TENS) for the prevention of migraine with aura [ 115 ,  116 ], \ncurrent evidence provides limited support for the routine use of neuromodulation \nin CM and, in particular, in MOH.\nPeripheral TENS has demonstrated a good level of evidence in episodic migraine \n[ 115 ], whereas only one open-label study has evaluated its use in patients with \nCM and concomitant MOH [ 117 ]. Despite the inherent limitations of the open-label \ndesign, 34.8% of patients achieved both a >50% response from baseline and \ndiscontinuation of MO.\nEvidence regarding transcranial direct current stimulation (tDCS) remains \nheterogeneous. A recent review found that tDCS may reduce migraine frequency, \npain intensity, and acute medication intake, without identifying a clear \nsuperiority between anodal and cathodal stimulation protocols [ 118 ]. Few studies \nhave specifically addressed MOH. De Icco  et al . [ 119 ] (2021) conducted a \ndouble-blind RCT with anodal tDCS applied for 5 days, targeting one of the \nprimary motor cortices (according to pain) during inpatient MO withdrawal. \nClinical follow-ups at 1 and 6 months showed a significant clinical benefit in \nthe active stimulation group. However, no concomitant reduction in acute \nmedication intake was observed [ 119 ]. In contrast, a three-arm RCT involving 135 \npatients with MOH compared anodal, cathodal, and sham tDCS, with a 1-year \nfollow-up, yielding overall negative results. The tDCS was delivered for five \nconsecutive days during drug withdrawal on the right primary motor cortex, using \nthe same stimulation parameters of the study by De Icco  et al . [ 119 ]. \nDespite the overall reduction of headache days over the 12-month period, the \nproportion of >50% responders did not differ significantly between groups \n(64.1% for anodal, 60.0% for cathodal, and 46.3% for sham) [ 120 ].\nCathodal occipital tDCS was found to be more effective than anodal dorsolateral \nprefrontal cortex (DLPFC) and sham stimulation in patients with MOH at two weeks \npost-intervention, particularly in reducing acute medication consumption [ 121 ].\nA further study explored the concomitant stimulation of two cortical targets in \na cohort of patients with CM and MOH who were resistant to multiple preventive \ntreatment lines and presented with major psychiatric comorbidities [ 13 ]. Anodal \nstimulation was applied to the right instead of left DLPFC (a montage previously \nused in other studies to reduce craving symptoms [ 122 ]), while cathodal \nstimulation targeted the occipital cortex. All patients experienced significant \nreductions in headache and migraine days per month, as well as acute medication \nuse. Notably, greater reductions in headache frequency were accompanied by \nimprovements in psychiatric symptoms [ 13 ].\nTranscranial magnetic stimulation (TMS), both single pulse (sTMS) and repetitive \npulse (rTMS), has also shown promise. In one study, sTMS was administered to 153 \ntreatment-resistant patients with high-frequency CM, with or without MOH. \nPatients received increasing doses of sTMS over three months, up to 6 pulses \nthree times daily. At 12-month follow-up, approximately 45% of patients achieved \nsustained clinical improvement, and the prevalence of MOH decreased from 52% at \nbaseline to 8% [ 123 ].\nIn a more recent study focused exclusively on MOH [ 124 ], 12 patients underwent \ninhibitory quadripulse repetitive TMS (rTMS) applied to the occipital cortex \ntwice weekly for one month [ 125 ]. This intervention resulted in a reduction of \napproximately 8 headache days per month, with patients reverting from CM to \nepisodic migraine and showing improved habituation.\nSeveral complementary non-pharmacological approaches, which remain underexplored \nin chronic headache and MOH, may be considered as adjuncts to standard treatment \nstrategies in MOH. Among these, dietary interventions are probably the most \nwidely recognized. Diet is known to influence migraine through mechanisms \ninvolving metabolism, gut microbiota, and systemic inflammation [ 126 ]. However, a \nstructured and systematic application of dietary interventions as a therapeutic \nstrategy in MOH patients is still lacking [ 127 ]. Recent findings suggest patients \nwith MOH more frequently present comorbid irritable bowel syndrome and that \ndopaminergic foods are more likely to trigger headache attacks in this \npopulation, whereas histaminergic foods appear to be more commonly associated \nwith migraine attacks in patients without MOH [ 128 ].\nIn parallel, overweight and obesity have been shown to be independently \nassociated with MOH even after multivariable adjustment for several confounding \nfactors ( e.g. , age, sex, and education level), with a proportional \nrelationship between increasing body mass index (BMI) and headache burden [ 129 ]. \nConsequently, weight loss in obese patients has been consistently associated with \nreductions in headache frequency and headache-related disability [ 130 ]. Some \ndietary approaches may be more effective than others [ 131 ], although concerns \nregarding long-term safety remain [ 132 ].\nOther complementary approaches, such as acupuncture and Ayurveda, may also be \nconsidered as adjunctive tools in MOH management, although evidence supporting \ntheir use and their underlying mechanisms remains limited.\nAcupuncture, a traditional Chinese medicine technique employed in several \nneurological disorders [ 133 ], has not yet been selectively investigated in MOH. \nRecently, it was evaluated as an add-on treatment to topiramate in a \nsingle-blind, double-dummy RCT, demonstrating favorable outcomes compared with \ntopiramate alone [ 134 ]. Furthermore, a recent network meta-analysis comparing \nacupuncture with topiramate and botulinum toxin type A (BoNT-A), found that \nacupuncture was not superior to BoNT-A in terms of efficacy [ 135 ]. Significant \nuncertainties remain regarding optimal treatment parameters for the delivery of \nacupuncture, including dosing, selection of target body points (among the 365 \nrecognized locations), treatment frequency, and the ideal number of sessions \n[ 136 ]. Ayurveda, a traditional Indian medical system, approaches migraine \nmanagement through interventions such as orally administered herbal preparations, \nas well as medicated oils applied nasally or used in therapeutic massage [ 137 ]. \nDue to the intrinsic challenges in standardizing Ayurvedic treatments, which are \ntypically tailored to the individual patient, rigorous investigation remains \ndifficult. However, novel research designs have been proposed to improve \nreproducibility in this field [ 138 ]. An important consideration in the potential \nuse of Ayurvedic therapies is the risk of herb-drug interactions [ 139 ].\n\nThe present article has several limitations that should be acknowledged. From a \nmethodological perspective, this is a narrative review and, therefore, subject to \ninherent limitations that must be considered when interpreting its findings. \nThese include potential selection bias in the literature search and limited \nreproducibility. Moreover, by their nature, narrative reviews reflect the \nauthors’ interpretation of the available evidence, rather than a systematic and \nquantitative synthesis. As a consequence, reviews conducted by other authors \nusing different methodologies may lead to partially different conclusions. From \nthe conceptual perspective, we deliberately adopted an inclusive approach toward \nnon-pharmacological interventions, including also trials conducted on CM \npopulation in which the exclusion of MOH patients was not explicitly stated, \ngiven the close epidemiological and clinical overlap between these conditions. We \nacknowledge that the joint consideration of CM and MOH populations may be \ndebated. While this approach allowed us to explore a broader range of potential \ntherapeutic strategies, the findings should be interpreted with caution, and \nfurther dedicated studies are required before these interventions can be \nroutinely implemented in clinical practice.\n\nPatients with MOH account for a large proportion of cases referred to headache \ncenters, and withdrawal of the overused medication remains the mainstay of \ntreatment. Nevertheless, relapse or treatment failure occurs in up to 50% of \npatients [ 140 ]. Current standard of care typically consists of withdrawal of the \noverused medication, brief educational interventions addressing the risks of MOH, \nand the initiation of pharmacological preventive therapies aimed at reducing \nmigraine burden and limiting dropout rates [ 3 ].\nIntegrating different non-pharmacological approaches and combining them with \npharmacological treatments may offer synergistic and more personalized \ntherapeutic effects in patients with MOH. Such interventions should be framed \nwithin a biopsychosocial model that accounts for individual psychological \nfactors, social context, and lifestyle habits [ 141 ,  142 ]. The concurrent \nimplementation of multiple non-pharmacological strategies may represent a \npromising avenue to improve treatment adherence and clinical outcomes in MOH \nmanagement. Further well-designed studies in this area seem both necessary and \nworthwhile.","source_license":"CC-BY-4.0","license_restricted":false}