Section 1
Medication overuse headache (MOH) is a secondary form of headache that
superimposes a chronic primary headache [ 1 ]. Specifically, MOH is diagnosed in
patients experiencing ≥15 headache days per month and using an excessive
number of symptomatic headache medications for more than 3 months [ 2 ]. Far from
being a rare condition, MOH accounts for approximately half of all visits to
specialized headache centers and affects over 70% of all patients with chronic
headaches [ 3 ]. However, MOH prevalence in the general population is significantly
lower, ranging from 0.5% to 7.2% across different countries [ 4 ]. This
discrepancy reinforces the idea that MOH and the overuse of acute medication
represent two clinical hallmarks of a more disabling headache, heralding poor
response to treatments [ 5 ]. MOH is directly related to both the type and quantity
of the overused acute medications. The threshold for “overuse” is defined as
≥15 days per month for nonsteroidal anti-inflammatory drugs (NSAIDs), and
≥10 days per month for other classes of medications including triptans,
combination analgesics, opioids, and ergot derivatives [ 4 ]. While it seems quite
robust that opioids and barbiturates have a higher chance of inducing MOH, the
role of triptans in causing MOH is still debated, although their threshold
remains precautionary lower than NSAIDs [ 6 ].
Beyond the type of acute medication used, several additional risk factors are
known to influence the development of MOH. It most commonly occurs in patients
with migraine as the underlying headache disorder, followed by tension-type
headache (TTH), post-traumatic headache, and new daily persistent headache [ 7 , 8 ]. In contrast, MOH development in patients with pure cluster headache remains
controversial. Moreover, female sex, low education, economic disadvantage, and
smoking are all associated with a higher risk of MOH [ 9 ].
Among the modifiable risk factors, metabolic syndrome, obesity, and physical
inactivity are strongly linked to MOH. Whereas the first two conditions are
generally associated with chronic migraine (CM), physical inactivity (defined as
<3 hours of vigorous physical activity per week) is specifically associated
with the risk of MOH [ 10 ].
Musculoskeletal pain and other co-existing painful conditions represent
additional risk factors for MOH. The relationship between multiple pain disorders
is so closely intertwined that recently ten conditions ( i.e. ,
musculoskeletal pain, temporomandibular disorder, fibromyalgia, irritable bowel
syndrome, vulvodynia, myalgic encephalomyelitis/chronic fatigue syndrome,
interstitial cystitis/painful bladder syndrome, endometriosis, and pelvic floor
pain) are now grouped under the term chronic overlapping pain conditions (COPCs)
[ 10 , 11 ].
Moreover, psychiatric comorbidities are more prevalent in MOH. Most notably,
depression and anxiety have been consistently reported [ 12 ], and in MOH patients
with multiple therapeutic failures, also bipolar disorder is quite common [ 13 ].
Furthermore, MOH patients tend to show different personality traits compared with
patients without MOH [ 14 ].
This result is also in line with new evidence showing that both childhood
emotional and physical trauma are strong determinants of the future development
of MOH. In particular, when childhood trauma is associated with the presence of
alexithymia, the risk of developing a somatization disorder increases [ 15 ].
The possible overlap between patients with MOH and those with substance use
disorder remains controversial. However, a seminal neuroimaging study has shown
that the orbitofrontal cortex remains metabolically hypoactive even after
withdrawal therapy, whereas other brain regions previously affected by MOH return
to a metabolic activity comparable to that of healthy controls [ 16 ].
A recent study suggests that CM patients could be divided into two categories.
On one side, “pure” CM with less comorbidities and risk factors, who have a low
risk of developing MOH and who can, in general, experience transient medication
overuse. On the other side, CM patients with multiple MOH risk factors, who are
more likely to develop MOH early in the course of migraine chronicity or to
relapse after withdrawal. In “pure” CM patients without prior history of MOH,
the annual incidence of MOH is approximately 17% per year, increasing to 33% in
those unresponsive to preventive treatments [ 17 ]. However, in patients with a
previous history of MOH, relapse rates increase up to 66–78% in the following
years [ 18 , 19 ].
Taken together, these data explain why the management of MOH has always
represented a complex issue in the headache field. For many years, it has been
debated whether a standardized detoxification strategy is necessary to interrupt
medication overuse (MO) or whether effective headache prevention alone may be
sufficient to avoid the development of MOH. This debate has become particularly
relevant in recent years with the introduction of new preventive medications,
which have reinforced the idea of avoiding formal detoxification [ 20 ].
While transient MO without progression to MOH can also occur in episodic
migraine (EM) patients [ 21 ], the development of MOH is typically accompanied by a
progressive increase in headache frequency, and by specific modifications of
neuronal excitability at peripheral and central level of the nervous system.
Notably, emerging evidence suggests that some of these modifications may be
partially reversible in the presence of protective factors [ 17 ].
Among the mechanisms implicated, central sensitization is probably one of the
most important processes involved in MOH, as demonstrated by neurophysiological
studies in humans [ 22 ] and mice models [ 23 , 24 ]. In humans, functional magnetic
resonance imaging (fMRI) studies reported findings consistent with central
sensitization, showing stronger pain-induced responses within the pain
neuromatrix and in several brain regions, including the motor cortex, superior
temporal sulcus, premotor cortex, supplementary motor area, lingual gyrus,
dorsomedial prefrontal cortex, anterior cingulate cortex, and primary
somatosensory cortex [ 25 ]. Compared with CM without MOH, those with comorbid MOH
exhibit more severe functional and structural alterations [ 25 , 26 ].
Encouragingly, these alterations seem to revert following recovery from MOH [ 27 ].
Due to the complexity of MOH presentations, a multidisciplinary, integrated
approach is increasingly viewed as a valuable strategy for management [ 28 ]. While
not all MOH patients may require such an approach, those with high relapse risk,
previous treatment failures, severe clinical burden, or psychiatric comorbidities
are likely to benefit from a combined therapy [ 28 ]. To date, however, several
elements of this approach remain insufficiently defined, including the specific
components of the intervention, involved specialties, and optimal composition of
the multidisciplinary team. In most studies, teams comprise neurologists,
psychologists, physiotherapists, and headache nurses, although some evidence also
supports the inclusion of occupational therapists, health educators, and aerobic
exercise trainers [ 29 ]. Another key consideration is the setting in which the
intervention is delivered. Current evidence suggests that outpatient or
day-hospital models offer comparable clinical effectiveness [ 30 ], while also
providing greater practicality and cost-efficiency [ 31 ]. An important exception
to an outpatient setting arises when patients present significant systemic
comorbidities, require withdrawal from drugs such as opioids or barbiturates, or
have previously failed outpatient detoxification attempts [ 32 ]. In addition, with
regard to the optimal duration of intervention, no consensus has been reached,
with available evidence ranging from 180 minutes to 96 hours [ 28 ].
The major advantage of non-pharmacological interventions lies in their
applicability even in presence of multiple comorbidities. In fact, they may be
especially beneficial for patients with conditions such as anxiety, depression,
asthma, obesity, or metabolic syndrome. These comorbidities not only predict
poorer outcomes [ 33 ], but represent per se an impediment to use some
pharmacological preventive therapies—either due to contraindications or
tolerability issues. For instance, beta-blockers are contraindicated in asthma,
valproate is discouraged in obesity, and topiramate should be avoided in patients
with suicide ideation.
Despite growing interest, multidisciplinary approaches for MOH have not been
systematically compared to other strategies of MOH management, with the exception
of a few studies [ 31 , 34 ]. Nonetheless, observational studies found responder
rates above 50%, ranging from 43% to 63% [ 29 , 35 , 36 ]. An open-label study
compared gradual detoxification to abrupt withdrawal combined with
multidisciplinary education. Both groups achieved a ≥80% success rate,
however the multidisciplinary education group required fewer staff resources and
needed fewer prophylactic drugs after detoxification [ 34 ]. A visual
representation of several non-pharmacological interventions used in the
multidisciplinary management of MOH is provided in Fig. 1 , while Table 1 (Ref.
[ 34 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]) summarizes and compares the main characteristics of the
included studies.
Visual representation of several non-pharmacological approaches
for the multidisciplinary management of MOH. Created in BioRender. Balordi M.
(2026) https://BioRender.com/tm0uc2b . EMDR:
eye movement desensitization and reprocessing; PNE: pain neuroscience education.
Cited articles for each non-pharmacological intervention.
MOH: medication overuse headache; RCT: randomized controlled trial; MIDAS:
Migraine Disability Assessment Score Questionnaire; QoL: Quality of Life; MHD:
month headache days.
Section 2
The present article is a narrative review of the literature on
non-pharmacological and multidisciplinary interventions for the management of
MOH. A narrative approach was selected instead of a systematic review or
meta-analysis because of the substantial heterogeneity of non-pharmacological
treatments and the wide variability of interventions in terms of intensity,
number, and frequency of sessions. In addition, many non-pharmacological trials
on CM or chronic TTH, often exploratory in nature, do not clearly report whether
patients with MOH were included or excluded. Given that a large proportion of
patients with CM also meet criteria for MOH, non-pharmacological studies on CM
were included unless it was explicitly stated that only patients with CM were
enrolled or that other primary headache disorders were excluded.
The research team conducted a structured non-systematic literature search
through PubMed/MEDLINE and Google Scholar databases. The search was conducted in
July 2024 and updated in May 2025. Keywords included combinations of terms such
as “medication overuse headache”, “MOH”, “non-pharmacological treatment”,
“multidisciplinary treatment”, “patient education”, “psychotherapy”,
“physical therapy”, “neuromodulation”, and “complementary medicine”.
We included peer-reviewed articles in English, published from 2000 up to May
2025, including selected earlier works of historical or clinical relevance.
Eligible studies involved adult populations and addressed non-pharmacological or
multidisciplinary interventions relevant to MOH. The research excluded studies
focusing exclusively on pharmacological approaches, pediatric populations, case
reports, and non-peer-reviewed publications.
Finally, findings were synthesized thematically and presented according to
intervention type. Given the heterogeneity of methodologies, no formal quality
assessment or quantitative synthesis was conducted.
Section 3
To date, the mainstay of MOH management remains the discontinuation of the
overused medication through withdrawal therapy that should be implemented even
when other therapeutic approaches are not possible, although recent evidence
showed that combing it with preventive therapy provides a better outcome
[ 48 , 49 , 50 ]. This may indeed be complemented by bridging analgesics and/or
prophylactic agents, if deemed appropriate. Nevertheless, further research is
warranted to optimize this strategy.
Withdrawal protocols vary also depending on the type of overused drug. Inpatient
management is recommended for patients overusing opioids, benzodiazepines, or
barbiturates, while outpatient detoxification is generally considered sufficient
for other medication classes [ 51 ]. The choice between abrupt withdrawal and
gradual tapering remains a topic of debate [ 52 ]. Gradual tapering is advised for
barbiturates and opioids to mitigate withdrawal symptoms, whereas for other
drugs, abrupt cessation appears more effective than gradual reduction [ 3 ].
Importantly, evidence suggests that structured detoxification program, when
paired with close follow-up, is highly effective [ 34 ]. Regardless of the modality
of medication interruption, sustained avoidance of medication overuse is
associated with improved medium- and long-term outcomes [ 53 , 54 , 55 ].
Bridging therapy with analgesics could be primarily offered to patients in the
outpatient setting, to increase patient compliance and as alternative to down
tapering alone. Long-lasting analgesics ( e.g. , naproxen) are the
drug-of-choice in bridging therapy for a couple of weeks. The duration of
bridging therapy is based on the duration of withdrawal symptoms, lasting for up
to 10 days for NSAIDs, around 4 days for triptans, and about 7 days for ergot
derivatives [ 56 ]. During hospitalization or day-hospital withdrawal [ 57 ],
intravenous administration of acetylsalicylic acid [ 58 ], or corticosteroids [ 59 , 60 ] may be used alone or in combination with supportive measures such as
hydration, antiemetics, clonidine, or benzodiazepines. Notably, corticosteroids
appear to be the most controversial choice among the possible rescue medications
[ 61 ].
Patient education represents a crucial component in the management of MOH [ 54 ].
Explaining, in accessible terms, what MOH is and how it develops enables patients
to adopt appropriate behaviors to discontinue MO, while at the same time
maintaining adherence to prescribed treatments. MOH education primarily aims to
inform patients about the role of acute medications in perpetuating headaches,
and to emphasize the importance of interrupting overuse in order to revert
chronicity and prevent recurrence. In the past, some seminal studies have shown
that, in patients with uncomplicated MOH, this “advice-only” approach can
achieve detoxification rates comparable to those of more intensive inpatient or
outpatient medication-based programs [ 50 , 52 ]. However, this net benefit cannot
be generalized to patients with complicated MOH [ 49 ].
Another critical issue in the management of MOH concerns the timing of
preventive therapy initiation—whether it should be started concomitantly with
withdrawal or delayed until after a period of withdrawal alone, typically lasting
three months [ 34 ]. This question remains unresolved and is generally addressed on
a case-by-case basis, taking into account factors such as previous failed
withdrawal attempts, headache burden, and the presence of comorbidities,
including psychiatric conditions [ 52 ]. Recent evidence suggests that preventive
therapy may be more effective than withdrawal alone, particularly following the
introduction of new migraine-specific preventive agents. However, the actual role
and magnitude of the effect of these medications in MOH management remain under
investigation [ 62 , 63 ]. Reported rates of MOH resolution with preventive
treatments ranges widely, from 29% to 88% of patients [ 64 ]. While some authors
propose that these new therapies may reduce the need for, or even allow the
omission of, formal withdrawal, others support the opposite approach [ 20 , 65 ].
One potential confounding factor in this debate is drug dosage, which may
differentially influence outcomes, as demonstrated for monoclonal antibodies
administered at different doses [ 66 ]. Further studies are needed to better
clarify the impact of calcitonin gene-related peptide (CGRP)-targeting monoclonal
antibodies in MOH management.
Due to the close relationship between the development of MOH and emotional
distress, dysfunctional thoughts, psychiatric and psychological comorbidities
[ 67 ], the pairing of pharmacological treatments with psychological support could
help patients with coping and prevent MOH relapses [ 68 ]. The European Academy of
Neurology endorsed Short-term Psychodynamic Psychotherapy (STPP) and mindfulness
as potentially helpful in MOH management [ 68 ].
STPP is a Freudian-inspired psychotherapy approach that considers migraine
headache as a psychosomatic disorder. It attributes the condition to the
patient’s previous traumatic experiences, suffering, and aspirations, which are
considered in terms of intra-psychic conflicts [ 69 ]. Mentalization—the ability
to process emotional conflicts and express them through words—emerges as a key
protective factor. This ability is shaped by a combination of personal and
environmental factors, with higher levels of mentalization linked to more
sophisticated and effective emotional regulation. In turn, this is associated
with a lower risk of psychosomatic symptoms and, consequently, a reduced
likelihood of migraine chronification. In a recent study, we found that in
accordance with the STPP model, CM and MOH patients tend to express low or
intermediate levels of mentalization, which may favor the development of chronic
headache symptoms. Therapeutic STPP aims at helping the patient to elaborate past
conflicts and the associated emotional burden, in order to get a resolution of
both intra-psychic conflicts and consequently headache symptoms [ 70 ].
Mindfulness, defined as a focused, non-judgmental awareness of the present
moment, has been investigated in migraine, but to date its real effectiveness is
under investigation since recent systematic reviews have not established a clear
benefit [ 71 ]. However, recent phase III trials involving 177 patients, reported
that mindfulness, when added to standard care ( i.e. , withdrawal,
education, and prophylaxis), led to greater improvements in terms of headache
frequency, medication intake and quality of life (QoL) [ 72 ].
Section 4
Besides the therapies and approaches discussed above, several emerging
non-pharmacological interventions may hold potential in the field of migraine
field and, in particular, in the management of MOH, given the complex clinical
presentation of these patients. However, most of these interventions have been
investigated only in recent years, with preliminary findings that are promising,
but limited in number and often lacking replication. Moreover, the available
evidence largely derives from studies conducted in the broader migraine
population, with only a few investigations specifically targeting patients with
MOH. As a result, the overall level of evidence supporting their efficacy in MOH
remains low. Nevertheless, owing to their favorable safety profiles, some of
these approaches warrant further investigation in future studies. In the
following section, a brief outline is provided regarding non-pharmacological
interventions that may represent potential adjuncts to standard therapy in the
management of MOH.
Among the most commonly used psychotherapeutic approaches, cognitive-behavioral
psychotherapy (CBT) is one the most extensively investigated in the field of
migraine, particularly in combination with other behavioral techniques. However,
its specific role in the management of MOH is less clearly defined than for other
headache conditions [ 73 ]. CBT aims to help patients process pain-related negative
emotions and dysfunctional thoughts, identify triggers, modify maladaptive
habits, and ultimately develop preventive coping strategies [ 74 ]. In patients
with MOH, CBT combined with other behavioral interventions has been evaluated in
a double-blind RCT, delivered by trained professionals during the withdrawal
phase, and was associated with MOH resolution in approximately 7% more patients
compared with standard therapy alone [ 75 ].
Another possible psychotherapeutic approach that may be of interest in the
management of MOH is Eye Movement Desensitization and Reprocessing (EMDR). This
technique is typically proposed as an adjunctive intervention within a
psychotherapeutic framework, primarily for the treatment of post-traumatic stress
disorder [ 76 ]. EMDR involves bilateral visual, auditory, and tactile stimulation
aimed at facilitating the desensitization and reprocessing of traumatic memories.
Two studies have investigated the use of EMDR in patients with migraine, without
detailed characterization of patient profiles (see review [ 77 ]). The two studies
differed in the modality of EMDR delivery, namely visual-only versus combined
visual–tactile stimulation. The first study focused on headache-related
traumatic experiences and reported that three months of EMDR were associated with
reductions in both headache days and acute medication use, with sustained
benefits at follow-up [ 77 ]. The second study, a larger RCT, showed that EMDR used
as an add-on to standard preventive therapy led to faster and more pronounced
pain relief [ 77 ].
Given the central role of patient education in the management of MOH, one might
speculate that a more structured and in-depth educational approach may be more
effective than brief or purely informational interventions, such as providing
short counselling or written materials. Pain Neuroscience Education (PNE) may
represent a valuable resource for implementation in patients with MOH. While
traditional biomedical education primarily focuses on tissue damage as the cause
of pain [ 78 ], PNE aims to enhance patients’ understanding of pain neurophysiology
and neurobiology, pain representation, and the meaning of pain. PNE is considered
a behavioral intervention that primarily targets coping strategies, which are
often dysfunctional in patients with migraine and MOH [ 79 , 80 , 81 ]. Indeed, PNE has
been shown to improve coping strategies and scores on the Central Sensitization
Inventory, Pain Catastrophizing Scale, and Tampa Scale of Kinesiophobia, even in
the absence of a direct effect on pain intensity [ 82 ].
Recently PNE has been implemented with promising results in several chronic pain
conditions, including cancer-related pain [ 83 , 84 , 85 , 86 ]. However, for other chronic
pain entities, including fibromyalgia and headache in general, the evidence
remains limited [ 87 , 88 , 89 ]. Recent reviews focusing on PNE in migraine have
reported moderate to strong evidence of effectiveness, although uncertainties
remain regarding optimal implementation parameters, including delivery modalities
and the number of sessions required [ 90 , 91 ]. At present, only a limited number
of trials specifically targeting MOH are available. However, several studies in
patients with CM, with and without MOH, are currently ongoing [ 92 , 93 ]. Although
the existing literature does not yet support the routine application of PNE in
the management of MOH, it is noteworthy that the benefits of PNE appear to be
enhanced when it is combined with other non-pharmacological interventions,
yielding better outcomes than single intervention alone ( e.g. , physical
therapy) [ 94 ]. Overall, these findings may suggest that PNE could be worthy of
further investigation in future MOH-focused studies.
Physiotherapy (PT) offers a broad spectrum of non-pharmacological interventions
for patients with migraine and MOH, including, among others, exercise programs,
manual therapy (MT), and dry needling (DN) [ 95 ]. Unfortunately, PT has only
recently been studied in the context of MOH with a single study by Trager
et al . [ 96 ]. This study analyzed data from the USTriNetX network
(covering over 124 million individuals) and found that patients who received MT
were less likely to develop MOH over the following 2-years, compared with those
who did not receive MT. The main rationale for PT in migraine, and MOH in
particular, lies in its ability to address musculoskeletal disorders
( e.g. , neck pain) contributing to headache symptoms [ 95 , 97 ]. PT
interventions in migraine may also include postural rehabilitation, balance
training, and vestibular exercises, while encouraging active patient engagement
and promoting lifestyle modifications [ 98 ]. Although the overall quality of
evidence is still low, a recent meta-analysis showed that specific combinations
of MT, exercise, and electrical stimulation can be effective in treating TTH
[ 99 ]. In migraine, more complex PT strategies—such as occipital transcutaneous
electrical stimulation, acupressure, osteopathic MT, soft tissue mobilization,
facial proprioceptive neuromuscular facilitation, and aerobic exercise—have
also demonstrated some efficacy [ 95 ].
For chronic headaches, MT hands-on techniques ( e.g. , massage therapy,
joint mobilization and spinal manipulation) could be valuable adjunctive
treatments [ 100 ]. Both soft tissue and articulatory MT have shown benefits in
migraines [ 101 ]. In particular, spinal manipulative therapy has been shown to
significantly reduce headache frequency and intensity in chronic headache, with
effects comparable to those of propranolol, topiramate, and amitriptyline [ 100 ].
However, uncertainties remain regarding standardized techniques to be used, the
optimal number of sessions, and the appropriate duration of treatment.
Aerobic exercise regimens are also included in the physiotherapeutic
armamentarium for migraine management [ 98 ]. Although in some cases physical
activity may trigger migraine attacks or exacerbate chronic pain, regular
exercise appears to reduce both migraine frequency and pain perception over time
[ 102 , 103 ]. Clinical guidelines from the French, Danish, and American Headache
Societies support the inclusion of exercise as part of migraine management
[ 104 , 105 , 106 ]. Accordingly, aerobic exercise and physical activity combined with
healthy lifestyle habits are classified as grade B recommendations for migraine
management [ 107 ]. In particular, strength training has been identified as the
most effective exercise modality for both CM and chronic TTH [ 108 , 109 ].
Moreover, both high- and moderate-intensity aerobic exercise have shown efficacy
comparable to that of topiramate and amitriptyline in migraine management [ 110 ].
Nevertheless, as in the case of MT, the application of exercise-based therapy
lacks standardization, and further research is required to define optimal
protocols and to account for variables such as patient preferences, fitness
levels, and psychological factors [ 111 ].
Dry needling (DN) is a puncture technique based on inserting needles into
painful areas, such as myofascial trigger points, sites whose stimulation is able
to elicit local and referred pain [ 112 , 113 ]. However, evidence on the efficacy
of DN for headache remains very limited, due to heterogeneous headache types or
lack of superiority over controls.
Non-invasive neuromodulation has been investigated over the past decade in the
context of migraine and CM. The rationale for its use lies in the potential to
reverse maladaptive neuroplastic changes underlying central sensitization and the
chronification process [ 114 ]. However, with the exception of single pulse
transcranic magnetic stimulation (sTMS) and peripheral transcutaneous electrical
nerve stimulation (TENS) for the prevention of migraine with aura [ 115 , 116 ],
current evidence provides limited support for the routine use of neuromodulation
in CM and, in particular, in MOH.
Peripheral TENS has demonstrated a good level of evidence in episodic migraine
[ 115 ], whereas only one open-label study has evaluated its use in patients with
CM and concomitant MOH [ 117 ]. Despite the inherent limitations of the open-label
design, 34.8% of patients achieved both a >50% response from baseline and
discontinuation of MO.
Evidence regarding transcranial direct current stimulation (tDCS) remains
heterogeneous. A recent review found that tDCS may reduce migraine frequency,
pain intensity, and acute medication intake, without identifying a clear
superiority between anodal and cathodal stimulation protocols [ 118 ]. Few studies
have specifically addressed MOH. De Icco et al . [ 119 ] (2021) conducted a
double-blind RCT with anodal tDCS applied for 5 days, targeting one of the
primary motor cortices (according to pain) during inpatient MO withdrawal.
Clinical follow-ups at 1 and 6 months showed a significant clinical benefit in
the active stimulation group. However, no concomitant reduction in acute
medication intake was observed [ 119 ]. In contrast, a three-arm RCT involving 135
patients with MOH compared anodal, cathodal, and sham tDCS, with a 1-year
follow-up, yielding overall negative results. The tDCS was delivered for five
consecutive days during drug withdrawal on the right primary motor cortex, using
the same stimulation parameters of the study by De Icco et al . [ 119 ].
Despite the overall reduction of headache days over the 12-month period, the
proportion of >50% responders did not differ significantly between groups
(64.1% for anodal, 60.0% for cathodal, and 46.3% for sham) [ 120 ].
Cathodal occipital tDCS was found to be more effective than anodal dorsolateral
prefrontal cortex (DLPFC) and sham stimulation in patients with MOH at two weeks
post-intervention, particularly in reducing acute medication consumption [ 121 ].
A further study explored the concomitant stimulation of two cortical targets in
a cohort of patients with CM and MOH who were resistant to multiple preventive
treatment lines and presented with major psychiatric comorbidities [ 13 ]. Anodal
stimulation was applied to the right instead of left DLPFC (a montage previously
used in other studies to reduce craving symptoms [ 122 ]), while cathodal
stimulation targeted the occipital cortex. All patients experienced significant
reductions in headache and migraine days per month, as well as acute medication
use. Notably, greater reductions in headache frequency were accompanied by
improvements in psychiatric symptoms [ 13 ].
Transcranial magnetic stimulation (TMS), both single pulse (sTMS) and repetitive
pulse (rTMS), has also shown promise. In one study, sTMS was administered to 153
treatment-resistant patients with high-frequency CM, with or without MOH.
Patients received increasing doses of sTMS over three months, up to 6 pulses
three times daily. At 12-month follow-up, approximately 45% of patients achieved
sustained clinical improvement, and the prevalence of MOH decreased from 52% at
baseline to 8% [ 123 ].
In a more recent study focused exclusively on MOH [ 124 ], 12 patients underwent
inhibitory quadripulse repetitive TMS (rTMS) applied to the occipital cortex
twice weekly for one month [ 125 ]. This intervention resulted in a reduction of
approximately 8 headache days per month, with patients reverting from CM to
episodic migraine and showing improved habituation.
Several complementary non-pharmacological approaches, which remain underexplored
in chronic headache and MOH, may be considered as adjuncts to standard treatment
strategies in MOH. Among these, dietary interventions are probably the most
widely recognized. Diet is known to influence migraine through mechanisms
involving metabolism, gut microbiota, and systemic inflammation [ 126 ]. However, a
structured and systematic application of dietary interventions as a therapeutic
strategy in MOH patients is still lacking [ 127 ]. Recent findings suggest patients
with MOH more frequently present comorbid irritable bowel syndrome and that
dopaminergic foods are more likely to trigger headache attacks in this
population, whereas histaminergic foods appear to be more commonly associated
with migraine attacks in patients without MOH [ 128 ].
In parallel, overweight and obesity have been shown to be independently
associated with MOH even after multivariable adjustment for several confounding
factors ( e.g. , age, sex, and education level), with a proportional
relationship between increasing body mass index (BMI) and headache burden [ 129 ].
Consequently, weight loss in obese patients has been consistently associated with
reductions in headache frequency and headache-related disability [ 130 ]. Some
dietary approaches may be more effective than others [ 131 ], although concerns
regarding long-term safety remain [ 132 ].
Other complementary approaches, such as acupuncture and Ayurveda, may also be
considered as adjunctive tools in MOH management, although evidence supporting
their use and their underlying mechanisms remains limited.
Acupuncture, a traditional Chinese medicine technique employed in several
neurological disorders [ 133 ], has not yet been selectively investigated in MOH.
Recently, it was evaluated as an add-on treatment to topiramate in a
single-blind, double-dummy RCT, demonstrating favorable outcomes compared with
topiramate alone [ 134 ]. Furthermore, a recent network meta-analysis comparing
acupuncture with topiramate and botulinum toxin type A (BoNT-A), found that
acupuncture was not superior to BoNT-A in terms of efficacy [ 135 ]. Significant
uncertainties remain regarding optimal treatment parameters for the delivery of
acupuncture, including dosing, selection of target body points (among the 365
recognized locations), treatment frequency, and the ideal number of sessions
[ 136 ]. Ayurveda, a traditional Indian medical system, approaches migraine
management through interventions such as orally administered herbal preparations,
as well as medicated oils applied nasally or used in therapeutic massage [ 137 ].
Due to the intrinsic challenges in standardizing Ayurvedic treatments, which are
typically tailored to the individual patient, rigorous investigation remains
difficult. However, novel research designs have been proposed to improve
reproducibility in this field [ 138 ]. An important consideration in the potential
use of Ayurvedic therapies is the risk of herb-drug interactions [ 139 ].
Section 5
The present article has several limitations that should be acknowledged. From a
methodological perspective, this is a narrative review and, therefore, subject to
inherent limitations that must be considered when interpreting its findings.
These include potential selection bias in the literature search and limited
reproducibility. Moreover, by their nature, narrative reviews reflect the
authors’ interpretation of the available evidence, rather than a systematic and
quantitative synthesis. As a consequence, reviews conducted by other authors
using different methodologies may lead to partially different conclusions. From
the conceptual perspective, we deliberately adopted an inclusive approach toward
non-pharmacological interventions, including also trials conducted on CM
population in which the exclusion of MOH patients was not explicitly stated,
given the close epidemiological and clinical overlap between these conditions. We
acknowledge that the joint consideration of CM and MOH populations may be
debated. While this approach allowed us to explore a broader range of potential
therapeutic strategies, the findings should be interpreted with caution, and
further dedicated studies are required before these interventions can be
routinely implemented in clinical practice.
Section 6
Patients with MOH account for a large proportion of cases referred to headache
centers, and withdrawal of the overused medication remains the mainstay of
treatment. Nevertheless, relapse or treatment failure occurs in up to 50% of
patients [ 140 ]. Current standard of care typically consists of withdrawal of the
overused medication, brief educational interventions addressing the risks of MOH,
and the initiation of pharmacological preventive therapies aimed at reducing
migraine burden and limiting dropout rates [ 3 ].
Integrating different non-pharmacological approaches and combining them with
pharmacological treatments may offer synergistic and more personalized
therapeutic effects in patients with MOH. Such interventions should be framed
within a biopsychosocial model that accounts for individual psychological
factors, social context, and lifestyle habits [ 141 , 142 ]. The concurrent
implementation of multiple non-pharmacological strategies may represent a
promising avenue to improve treatment adherence and clinical outcomes in MOH
management. Further well-designed studies in this area seem both necessary and
worthwhile.
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