Clinical presentation of MOH varies between patients and even changes with time in the same patient. There can be an increase in the frequency of a pre-existing headache or the evolution into a new type of a headache. There are no specific tests to diagnose this condition, and thus it is headache quantity and frequency, and type and frequency of acute medication used that leads to the diagnosis. Although pain location and quality are non-specific in MOH, there are some general features commonly seen in this patient population; these include the following:

• A headache is usually episodic
• Frequent acute medication consumption depends on the type of abortive medication used (see Etiology section for more detail)
• Neck pain is common (often mistaken for a cervicogenic headache, which in turn tends to be resistant to cervicalgia-appropriate treatments)
• Typically occurs in the morning (presumed related to withdrawal occurring during sleep)
• Poor sleep
• Autonomic symptoms (i.e., nasal congestion, rhinorrhea, gastrointestinal [GI] disturbance) are more frequent with overused opioids
• Comorbid anxiety and depression
• All headache treatments are generally less effective when MOH is present; efficacy improves after the weaning.

There are currently no specific biomarkers or studies whereby differentiate or point towards MOH. The diagnosis is purely clinical and deserves a special attention not to be overlooked due to the potential consequences of worsening over time.

Typical treatment involves weaning the patient off the overused acute headache medication while simultaneously focusing on preventative treatment. Several studies show that complete 100% weaning of overused acute medication shows the best results compared to continuing on the same acute medication responsible for MOH but placing frequency limits on its use. Note that patients can be prescribed a new acute medication from a different class. Patients can wean from the offending medication abruptly ("cold turkey") or gradual over several weeks. Preventative treatment can include prophylactic medication and/or non-pharmaceutical treatments (i.e., cognitive behavioral therapy, biofeedback, relaxation training, lifestyle modification with trigger avoidance).[8][9][10]

Educating the patient and their family on the importance of limiting acute medication use is vital in preventing MOH. Initial worsening of a headache within the first few days of weaning is fairly common. Withdrawal symptoms are thought to typically last up to 10 days then eventually followed by improvement in MOH. Weaning patients off MOH-related medication can be done in an outpatient or an inpatient setting. Most cases can be managed as outpatient mainly through educating patients to cut down their acute medication use. It is important to address and treat co-morbid psychiatric conditions, especially anxiety and depression which are often associated with MOH, but without potentiating the boosting effects of anxiolytic medication has in maintaining the headache.

Following successful weaning, about half of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's MOH had resolved, tapering them off of the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year. [11][12]

MOH occurs in patients with an episodic primary headache, and thus chronic versions of an episodic headache are one of the main differentials. Other secondary headaches must be ruled out, with the guide of the clinical picture and the aid of all the necessary tests, and more so when the features of the original episodic headache are different from its chronic counterpart.

The results of a tailored regime are excellent in the long-term, but with an estimated relapse rate of about 30% within 6 months and 50% following a 5-year period.

Practitioners contend that frequent use of acute headache medications may be a reflection of poorly controlled headaches, and not necessarily the cause. This idea stems from evidence that not all patients improve when they stop taking headache-relieving medications. Instead of primarily blaming analgesic medication overuse as the reason for the increase in headache frequency, clinicians must be cautious in their approach to managing these patients and not to overlook those in whom headaches are simply poorly controlled. Some studies suggested that other substances, such as the regular use of tranquilizers or other recreational substances abused in the general population, should be considered in conjunction with analgesics.

The diagnosis and management of medication overuse headache is complex and best done with an interprofessional team that includes a neurologist, pharmacist, internist and the primary care provider. The key is to educate the patient and family on the importance of limiting acute medication use is vital in preventing MOH. The underlying psychiatric condition must be addressed and a referral to a mental health professional can be helpful.

Following successful weaning, about half of patients relapse after 5 years; thus, it is essential to have the patient follow-up regularly. Once the patient's MOH had resolved, tapering them off of the preventative medication may be considered. There are no specific guidelines, but some professionals suggest tapering prophylactic medication after 1 year.