1. Introduction

Headache disorders are common disabling conditions and include tension-type headache (TTH) and migraine ^[1]. Most persons have experienced at least one episode of headache in their life course. Indeed, headache disorders are the second and third most prevalent disorders in the world ^[1]: 62.2% of the adult population is affected by episodic tension-type headache (TTH), 14.7% by episodic migraine, 3.3% by chronic tension-type headache (CTTH), and 2% by chronic migraine (CM). In a few studies carried out on the pediatric population, it is possible to observe a lower prevalence of these diseases, which, however, remains quite high (9.2% for migraine, 15.9% for TTH, and 0.9% for CTTH) ^[2][3][4].

Headaches, and migraines in particular, are complex diseases in which psychological, social, and biological aspects are closely connected. In this perspective, a biopsychological intervention seems the most appropriate to manage this condition adequately and this is determined by different components: proper diagnosis, patient education, multidimensional assessment, strategic intervention including different approaches, according to the assessment and patient’s needs, changes monitoring, and follow-up ^[5][6].

Headache management includes drug treatments such as non-steroidal anti-inflammatory drugs, triptans, as well as prophylactic drugs (e.g., amitriptyline, topiramate, onabotulinum toxin-A, and β-blockers), and new drugs such as anti-CGRP monoclonal antibodies ^[7]. The phenomena of tolerance and pharmacoresistance to common preventive pharmacological therapies can make the pharmacological treatment of chronic headaches complex ^[8], which is sometimes associated with side effects and complex interaction between different drugs.

Therefore, new headache treatment options need to be found. In recent decades, innovative non-invasive neuromodulatory techniques, for example, transcranial magnetic stimulation (TMS) and supraorbital nerve stimulation (SNS), which have shown remarkable results, have been developed ^[9]. In recent years, complementary and alternative medicine (CAM) has been found to be a compelling option for headache disorders ^[10][11]. CAM includes several practices and products of the health care system, which are considered complementary or supplementary to conventional techniques and therapies. Finally, behavioral approaches are emerging as promising treatments to change maladaptive behavior and ways of thinking that could enhance headache-related burden and pain.

Within a biopsychosocial approach, a multidisciplinary program for headache management should be planned. It should include not only conventional pharmacological therapies but also: patient education and support, lifestyle modification (diet, physical activity, lifestyle habits, stressful conditions, etc.), and complementary measures. These may include nutraceuticals, neuromodulation techniques, behavioral approaches, and psychotherapy intervention when necessary ^[12][13][14].

Non-pharmacological interventions may be useful to help patients manage pain and they are usually well tolerated. The use of these methodologies is suggested for specific categories of patients, such as pregnant women and adolescents, and also when the use of drugs must be limited or avoided due to contraindications, excessive use, or known side effects ^{[4][15][16][17][18][19]}. 

2.  Non-Invasive Neuromodulation

Although neuromodulation techniques were initially invasive, advances and pro-gress in technology have led to more sophisticated and less invasive devices with bet-ter safety and efficiency^[9].

The first neuromodulation approach analyzed in this review used deep brain stimulation (DBS), targeting the hypothalamus, for cluster headaches ^[20]. Subsequently, to reduce the risk and invasiveness of neuromodulation, the sphenopalatine ganglion ^[21][22][23] and the occipital ^[24][25], supraorbital, and auriculo-temporal ^[22] nerves were targeted, in cluster headaches and also in migraines. With technological innovations, which have led to further improvements of these techniques in terms of efficacy, safety, and reduced invasiveness, it has been possible to use neuromodulation even in patients who had comorbidities or contraindications to traditional pharmaco-logical treatment.

3. Nutraceuticals

Nutraceuticals include “natural” substances such as vitamins, minerals, and herbal remedies that may be less toxic than drugs. Some of these remedies appear to be effective and promising in the management of chronic pain but most current studies are underpowered or show inconsistent results ^[19]. Recently, the use of nutraceuticals has been expanding as an aid in the treatment of headache disorders in adults who prefer these approaches over traditional drug remedies.

Guidelines from the American Academy of Neurology (AAN), American Headache Society (AHS), the Canadian Headache Society (CHS), and the European Federation of Neurological Societies (EFNS) discussed the use of nutraceuticals in migraine prophylaxis, sometimes reporting conflicting recommendations ^[18].

4. Behavioral Approaches

Behavioral approaches to headache consist of treatment interventions which are intended to modify maladaptive behaviors and thoughts that could increase headache-related burden and pain. There is evidence of the efficacy of behavioral interventions in the management of primary headache disorders in adults and children, particularly for migraine, both in episodic and chronic forms.

Behavioral approaches have proved to produce sizeable effects on headache frequency and to have a valuable impact on some patient-reported outcomes such as disability, quality of life, depression, anxiety, self-efficacy, and medication intake ^[4]. Recent reports show that the efficacy of behavioral approaches for headache makes it possible to consider them not just as alternative or complementary to pharmacotherapy, but as valid treatment options, with a comparable efficacy ^[26]. Moreover, the combination of pharmacological and behavioral therapies showed higher effectiveness compared to single approaches, i.e., compared to pharmacotherapy alone or behavioral therapies alone ^[26].

Different mechanisms of action of behavioral treatments, which reasonably act in combination, have been hypothesized. Behavioral treatments have an effect both on headache itself and on the concomitant conditions of distress and psychiatric symptoms that are frequent in chronic headache patients and commonly associated with poor prognosis. Behavioral treatments reduce stress, increase self-efficacy, and reduce the external locus of control. The combined effect of different factors could stimulate a change in the way patients perceive and experience pain, which in turn can lead to an improvement in symptoms ^[4][26][27]. At the biological level, these treatments seem to produce functional modifications in the brain areas and systems responsible for the perception and regulation of pain ^[4][27].

Recently, behavioral treatments are also becoming increasingly popular because conventional treatments are often considered by patients to be ineffective ^[4][19]. The use of behavioral treatments is common in clinical practice, mostly in specialized units such as headache centers that provide innovative treatments ^[4][19]. One of the barriers to the spread of these interventions is the need for neurologists or psychologists specialized in the use of behavioral techniques, which constitutes a cost, particularly if therapies are conducted individually and not in a group. Therefore, although there is much evidence of the effectiveness of behavioral approaches, these interventions are not widely used in clinical practice ^[27]. Moreover, the lack of a standardized treatment protocol in psychological treatment and the consequent diversity and heterogeneity of the specific protocols sometimes make it difficult to draw meaningful conclusions^{[26] [28]}.