Frieda Wiley, PharmD, BCGP, is a writer and pharmacist. 

Frieda Wiley, PharmD

It is no secret that psychiatric conditions may predispose individuals to various comorbidities, including migraines. Similarly, patients with migraines tend to have a higher risk of developing psychiatric complaints.

The complexity of treating migraines is amplified when the patient also has psychiatric comorbidities. The spectrum of presentation and symptomatology in this population subset creates a prime opportunity for pharmacists to make sizeable contributions in managing these conditions.

Migraine Management Inundated with Complexity, Challenges

Migraine management in patients with psychiatric conditions must take into account the complications that plague both disease states.

“Compliance and adherence are the biggest pitfalls because studies have shown that patients [with psychiatric conditions] are more likely to over- or underuse [medications],” said 

, a postdoctoral fellow in the department of pharmacy practice and translational research at the University of Houston College of Pharmacy in Texas.

Both disease states can have severe consequences. Taking a nonsteroidal anti-inflammatory drug (NSAID) or triptan either more frequently than prescribed or at a higher dose can trigger migraines—a phenomenon known as medication overuse headache.

Conversely, medication underuse has its own set of hurdles, which El-Desoky finds particularly challenging when trying to optimize therapy in patients with migraines. Such is the case with prophylactic migraine therapy, which typically takes 4 to 12 weeks before symptoms start to improve. Often discouraged by not experiencing immediate results, many patients either stop taking prophylactic medications regularly or discontinue them altogether.

Poor adherence can give rise to a prescribing cascade, and the increasing complexity of the patient’s drug regimen can often worsen outcomes. Because patients with psychiatric conditions often have multiple prescriptions, adding migraine therapy can become a delicate balancing act when trying to prevent issues related to polypharmacy.

“The key here is to optimize the patients’ medications and decrease the pill burden,” El-Desoky said. She recommends choosing a preventative migraine medication that also can address other comorbidities the patients have. Venlafaxine makes a good choice for a patient who has posttraumatic stress disorder in addition to migraines. Nortriptyline and amitriptyline ease insomnia and depression as well as migraine symptoms.

Some medications routinely used in migraine management are not appropriate for certain psychiatric conditions. For instance, β-blockers and the calcium channel blocker verapamil can worsen depressive symptoms and should be avoided in patients with depression, according to Lama Al-Khoury, MD, associate clinical professor of neurology 

at the University of California, Riverside, School of Medicine.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) should be avoided in patients who have bipolar disorder because they can trigger hypermanic episodes. Instead, a mood stabilizer such as divalproex sodium (Depakote) may be a better choice. Al-Khoury warns against the use of divalproex in women of childbearing age because of its teratogenicity.

Medications that can potentiate serotonergic effects, including serotonin syndrome, should be avoided or used with care in patients with migraines. Al-Khoury advises pharmacists to educate patients taking antidepressants/serotonergic medications to limit using abortive therapies such as triptans to no more than 2 days per week to prevent their serotonin levels from surging to dangerous limits. El-Desoky encourages pharmacists also to look for less-obvious culprits such as cyclobenzaprine and tramadol.

Experts say pharmacists have numerous opportunities to enhance patient care in this patient population.

 Even when questioned directly, a patient’s migraine or psychiatric condition can affect their ability to remember their medication history. As a result, they may forget to mention a medication or supplement. The negative stigmas associated with migraine and psychiatric conditions may cause some patients to omit the frequency of intake. Pharmacists’ access to prescription records and their increased patient interaction can help bridge the gap. 

“It’s always appreciated when pharmacists flag potential interactions in patients who may not be as forthcoming with all [their] medications, along with the frequency and dosing,” said Cristina Wohlgehagen, MD, a headache specialist and neurologist at Texas Health Presbyterian Hospital Dallas.

. The accessibility and frequent patient-clinician interaction make pharmacists excellent resources for providing patient information. Pharmacists can remind patients about potentially bothersome symptoms and teach them to recognize signs of harmful adverse effects (AEs).

The teaching aspect proves particularly critical with regards to improving adherence. El-Desoky urges her colleagues to ensure patients understand the importance of taking prophylactic medications regularly as prescribed and emphasizing it may take up to 12 weeks before their symptoms improve. Patients should leave the encounter understanding the importance of not skipping doses.

 Both El-Desoky and Al-Khoury encourage patients to keep headache diaries to document the frequency, time, and resolution of their migraines.

Consider nonpharmacological options when possible.

 “Pharmacological therapy is not appropriate for every patient—especially patients [with psychiatric conditions] who are already taking many medications and struggle with [adherence],” Al-Khoury said.

In some cases, this might entail investigating underlying causes of a patient’s migraines. Stress triggers migraines in 70% of those with the condition.

Patients facing insomnia and sleep disruption may benefit from a sleep study. “Sleep is critical, and a sleep study should be conducted when obstructive sleep apnea is suspected because you can sometimes avoid medications in these patients,” Al-Khoury said. Helping patients modify their daily habits, lifestyle, and sleep may be the only tool they need to gain control of their migraines. Al-Khoury sometimes uses melatonin or other insomnia treatments in patients with migraines and insomnia. 

 Migraine management in patients with psychiatric disorders is highly complex and variable. Clinicians should customize treatment based on the individual patient’s comorbidities, preferences, socioeconomic situation, lifestyle, and other circumstances.

Enacting weight management strategies is especially important in patients who are depressed and have poor body image. It may make sense to avoid initiating antimigraine therapies that also cause weight gain in patients who are already overweight. Tricyclic antidepressants should be avoided in such patients. If patients suffer from migraines in addition to depression and anxiety, venlafaxine makes a suitable substitution, as it is less likely to cause weight gain. Duloxetine and gabapentin should be avoided altogether.

 Monitoring is critical in this patient population, as many medications have bothersome AEs or other challenges. For example, high-dose venlafaxine therapy can raise blood pressure, and the pharmacist should follow up with patients when they refill their prescriptions or visit the pharmacy for other reasons.

Similarly, pharmacists’ recurring patient encounters offer numerous opportunities to assess the patient’s progress and reinforce adherence. El-Desoky recommended encouraging patients to use pill boxes and medication organizers. Although mobile device apps, phone messages, and alarms can also serve as helpful reminder tools, El-Desoky noted that her patients experienced greater benefit from making medication charts.

“I’ve made charts for patients to check off whether they took their meds,” she said. “From what I’ve seen, visual aids tend to be the most effective in helping people remember to take their meds.”

Despite the continued push toward collaborative practice, the health care industry remains largely fragmented regardless of the profession. Even with the prevalence of migraines in patients with psychiatric conditions, fewer than 1% of psychiatrists treat them.1 Similarly, pharmacist-physician interactions generally remain rare.

“I have rarely seen multidisciplinary interactions between pharmacists and physicians outside large academic facilities where you tend to have neurologists, psychiatrists, and pharmacists on board,” Al-Khoury said.

Despite this hurdle, El-Desoky seems optimistic and encourages pharmacists to capitalize on in-pharmacy services and any other opportunities to demonstrate their value and ability to educate patients and other health care professionals.

“Every facility has an opportunity for pharmacists and other practitioners to present their knowledge,” she said. “Tell them, ‘I’m here and able to help.’”

Cascade E, Kalali A, Smitherman T. Treatment of migraine and the role of psychiatric medications. 

The basics of headache medication & overuse. The Migraine Foundation. June 11, 2016. Accessed October 1, 2020. 

https://americanmigrainefoundation.org/resource-library/medication-overuse-headache/

Maleki N, Becerra L, Borsook D. Migraine: maladaptive brain responses to stress. 

2012;52(suppl 2): 102-106. doi:10.1111/j.1526-4610.2012.02241.x

Articles

Add value by optimizing medications, decreasing pill burden.

Pharmacists Can Help Manage Migraines in Patients With Psychiatric Conditions

The correlation between obesity and various diseases (eg, cardiovascular disease, certain cancers, diabetes, etc) points to a growing public health crisis. Obesity is a leading risk factor for developing type 2 diabetes, thus offering tremendous opportunity for pharmacists to improve patient outcomes.

Patients now have a variety of options to help them lose weight. These include pharmaceuticals, invasive surgeries, minimally invasive implants and devices, and lifestyle modifications such as diet and exercise.

 Similarly, health and wellness services in pharmacy have surged in recent years, with pharmacists offering a variety of specialized services to support their patients’ needs.

Although counseling patients at the time of medication dispensing seems the most obvious time to educate on weight-focused wellness, it is frequently not practical.

Some pharmacists carve out time slots dedicated to addressing individual patients’ needs by scheduling appointments. Planning is key, according to Christina Madison, PharmD, FCCP, AAHIVP, founder and CEO of The Public Health Pharmacist and associate professor of pharmacy practice at Roseman University of Health Sciences in Las Vegas, Nevada.

Educating patients during a consultation is the single most important service pharmacists can offer. What follows are several weight-management counseling points for patients with diabetes:

> Encourage patients to eat a whole foods diet. "If it doesn't walk, swim, run, come from the ground, and it didn't exist 100 years ago, don't eat it," said Harris. In other words, enourage patients to avoid processed foods and any foods that have chemical ingredients that "you would need a PhD to pronounce."

> Educate patients on how to eat for weight loss. Madison recommended that pharmacists drive home to importance of limiting noncomplex carbohydrates and avoiding foods high in sugar. Proper fluid intake is also important.

> Groom the patient for success. "Making lifestyle changes is more easily said than done for people whose lifestyle is not currently aligned with these recommendations," Bisher cautioned. "This is why I always recommend starting off with small changes, so the person can feel successful implementing them." For example, focus on adding foods that are more ideal for their situation rather than suggesting the complete avoidance of certain foods. 

> Consider the patient's work schedule, home environment, sleep schedule, social interactions, and stress management. Discuss these factors with the patient and adjust their wellness plan accordingly. 

> Encourage patients to get moving. Madison stressed that patients should aim for a minimum of 30 minutes of physical activity 5 days a week. Harris enacted the 20-8-2 method, which has patients sit for 20 minutes, stand for 8 minutes, and then walk for 2 minutes.

Madison describes the ideal scenario as a private space where the pharmacist has allotted 15 to 20 minutes during an off-peak period. She encourages pharmacists to document the encounter and follow up with the patient, which includes recording the patient’s weight before the encounter and at follow-up.

Richard Harris, MD, PharmD, MBA, founder of Great Health and Wellness in Houston, Texas, noted that some pharmacists use these assigned times to conduct wellness checks, review medications, or discuss other issues the patient may be facing.

“There are some pharmacists and pharmacies that offer specific weight- loss programs,” Harris said. “They’ll do functional medicine, which is getting to the root cause of the issues, as well as holistic, lifestyle, or integrative medicine.”

Brian Bisher, PharmD, BCPS, a clinical pharmacist and an Institute for Integrative Nutrition–certified health coach in Cincinnati, Ohio, works at an area hospital that provides some of these services.

“I would label our clinic as a pharmacy-run service that offers weight-loss/nutrition services,” he said. “We set aside 30- to 60-minute appointments specifically for diabetes patient care management in our outpatient wellness clinic.”

Bisher’s clinic sometimes recruits a registered dietician as well. However, unlike some community practice settings, patients cannot receive such services without a referral from their physician.

According to Harris, many pharmacies that offer these specialized services also carry high-quality, pharmaceutical-grade supplements—a feature he feels is critical, given the fact that OTC dietary health supplements are not regulated to the same degree of stringency as prescription pharmaceutical products.

“These are high-quality supplements you can trust,” Harris said of the supplements typically carried at pharmacy wellness centers. “There are plenty of these wellness centers out there, and the pharmacies that have these wellness centers are the ones I highly recommend people seek.”

Although they had different opinions about which supplements to stock in the pharmacy, Harris and Bisher did agree on a few products, namely, berberine. “Berberine is a supplement that can be used in place of metformin to start if a patient would prefer to use herbal therapy,” Bisher explained.

Results of a 2012 meta-analysis and systematic review concluded that berberine effectively treated hypoglycemia

 However, more studies are needed to evaluate the safety of berberine in long-term use.

Berberine is an isoquinoline alkaloid compound isolated from rhizoma coptidis. Its hyperglycemia-mitigating effects were first documented in 1988 when it was used to treat diarrhea in patients with diabetes, and the extract’s antidiabetic potential has since been studied in a variety of clinical trials.

However, a search in ClinicalTrials.gov using the key words “berberine” and “diabetes mellitus type 2” only resulted in 5 studies on berberine. Two of those studies explored the compound’s effect on diabetes (NCT02084004 and NCT00425009). The first study was withdrawn, and the second study was completed in December 2004.

A different trial helped illustrate berberine’s clinical potential. The pilot study was divided into 2 studies with the goal of evaluating the safety and efficacy of berberine in patients with type 2 diabetes.

In study A, 36 adults who had received a recent diagnosis of type 2 diabetes were randomly assigned to receive either berberine or 0.5 g of metformin 3 times per day for 3 months. Berberine’s hypoglycemic activity mirrored that of metformin with statistically significant decreases in hemoglobin A1C (HbA1c; from 9.5% ± 0.5% to 7.5% ± 0.4%; P < .01). Patients in the berberine arm also experienced significant decreases in fasting blood glucose (FBG), postprandial blood glucose (PBG), and plasma triglycerides.

Forty-eight patients with poorly controlled type 2 diabetes were enrolled in the second study (study B) and received berberine supplements for 3 months. Similarly, biomarkers for blood sugar improved. FBG and PBG improved within 1 week and HbA1c dropped (from 8.1% ± 0.2% to 7.3% ± 0.5%; P <.0001).

Although patients in the berberine arm did not lose weight, they experienced a redistribution of body fat. However, some data suggest that, like metformin, berberine may result in weight loss.

Despite the supplement’s benefits, Bisher does not foresee berberine replacing metformin.

In addition to berberine, Harris and Bisher also recommended stocking the following supplements that may help patients with weight management:

Magnesium: This mineral is responsible for more than 300 biochemical reactions in the body and an important cofactor for energy generation and metabolism.

Zinc: “Zinc deficiencies are associated with metabolic derangments,” Harris said.

Chromium: This mineral helps the body process sugars and facilitate insulin’s activity.

Vanadium and cinnamon help improve insulin sensitivity.

Patients now have a variety of options to help them lose weight, and pharmacists can offer a variety of specialized services to support their patients’ needs.

Pharmacists Offer Tips on Weight Management in Diabetes

The term vasculitis refers to a rare and complex family of diseases that can cause inflammation of the aorta and other arteries, veins, and blood vessels. Vasculitis manifests in many forms, involving different parts of the body and presenting with a diverse range of severity and duration.

Kawasaki disease (KD),a form of vasculitis that is exclusive to children,is known to inflame blood vessels throughout the body, especially those feeding the heart. Currently, the CDC is investigating reports of multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) in children, which may present with KD-like features.

Recent studies suggest that, although rare, KD may be triggered by underlying infections such as COVID-19 or flu.

 KD produces clinical signs such as prolonged fever; swollen lymph nodes; bloodshot eyes sans drainage; rash; red, cracked lips and tongue; swollen lymph nodes on 1 side of the neck; and a fever of 100.4 °F or more that persists for 5 days or longer. KD typically occurs in children under 5 years of age but can also affect older children.

The coronavirus family has been suspected of playing a role in the onset of KD for the past 2 decades. In a 2005 study, a group of researchers in Connecticut, identified a novel strain of the disease, human coronavirus New Haven, in the respiratory secretions of 8 of 11 children who had KD versus 1 out of 22 controls.

COVID-19 was initially pegged as a disease that primarily affects the respiratory system. However, that changed with news of potential cutaneous involvement in certain populations in Italy in spring 2020, following reports of strange lesions on children’s skin. The results were published in The Lancet in May 2020. The Italian province of Bergamo, which had the highest number of COVID-19 infections and deaths in the Mediterranean country, experienced a 30-fold increase in incidence compared with the monthly incidences recorded during the previous 5 years.

During the month of April, investigators observed an increased incidence of what they referred to as “Kawasaki-like disease.” Between February 18 and April 20, 2020, 10 children (aged 7.5 years [SD, 3.5]) received diagnoses of KD. Children were admitted to the hospital and, on average, presented with fever on day 6 (range, 4 to 8). Half the patients presented with typical manifestations of KD, including cutaneous involvement such as polymorphic rash; hand and feet anomalies such as firm induration, erythema, or both; and nonexudative conjunctivitis. Investigators observed altered appearance of the lips and/or oral cavities of 80% of patients. The remaining 5 patients presented with incomplete forms of KD.

However, truly discerning the connection between COVID-19 or other members of the coronavirus family requires additional study.

KD manifestations often resolve on their own, and many children recover fully. However, children who fail to receive appropriate medical evaluation and treatment face heart damage and other complications. Because no specific test can diagnose KD, a fever lasting for more than 5 days is often used as an indicator of potential disease. To help determine whether a patient has KD, a physician might run blood and urine tests, an electrocardiogram, and an echocardiogram.

KD has 2 primary treatments: prolonged aspirin therapy, initiated every 6 hours and then decreased to once-daily dosing, and intravenous immunoglobulin to curtail swelling in blood vessels.

Vasculitis. American College of Rheumatology. Updated March 

https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Vasculitis

Kawasaki disease (KD). American College of Rheumatology. March 2019. Accessed May 28, 2020. 

https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Kawasaki-Disease-KD

Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study. 

 2020;395(10239):1771-1778. doi:10.1016/S0140-6736(20)31103-X

A Kawasaki-like inflammatory disease has affected children who have coronavirus disease 2019.

Investigators Find COVID-19 Connection in Vasculitis

An estimated 32 million individuals 12 years and older used psychedelic medicine in the United States in 2010, according to a US population survey. As the opioid epidemic has eclipsed concerns about illegal drugs in recent years, the medical community and the federal government alike have begun reexamining certain illicit drugs as potential alternatives to opiates in pain management.

Perhaps no other "illicit" substance has played a greater role in turning the tides recently than medical cannabis. Its slow but steady serial legalization and decriminalization at the state levels to treat a variety of complaints, including pain, have helped bring cannabis, cannabis products, and other stigmatized  drugs to the forefront.

"It is most surprising that even though cannabis has been used for a number of ailments for thousands of years—even dating back to the 28th century BC—it is now being recognized as a valid treatment option," said Swathi Varanasi, PharmD, an integrative health pharmacist and medical cannabis consultant in Los Angeles, California. "However, because of the way cannabis has been criminalized, it hasn't been integrated into standard treatment algorithms.'

Regulatory measures aside, pharmacists and other members of the medical profession often wrestle with safety when assisting patients who use cannabis for medicinal purposes. Cannabis has been studied extensively for numerous uses, including its potential benefits in neuropathic pain, chronic pain, and inflammation. A 2014 study found that most patients cited relief from chronic pain as the most common reason for their medicinal use of cannabis. Yet the plant's psychoactive properties continue to draw concerns regarding abuse potential, owing to the effects of 1 phytochemical, Delta-9-tetrahydrocannabinol, known for its psychoactive properties.

However, these are not the only challenges pharmacists face when it comes to assisting patients. "The biggest pitfall in advising patients on cannabis is that dosing is so difficult to standardize," Victoria Starr, RPh, a cannabis pharmacist at SageLife, LLC, in Portland, Oregon, told 

Cannabis for medicinal purposes is highly complex, largely because of its high number of phytochemicals, called constituents. To date, the plant has been found to contain more than 560 constituents. When individuals consume these as the whole plant, the chemicals ofery synergistic and therapeutic benefits while mitigating potential toxicities, what's known as the entourage effect. Synthetic cannabis typically contains only 1 active ingredient and lacks additional chemicals that can help regulate undesirable effects. However, customizing cannabis dosing to even the individual patient is no small feat.

"Besides attaching medical benefits to each of these components, the combination of synergistic benefits needs to be determined, along with the proper ratio and dose," Starr explained. "So unlike Western medicine, in cannabis, there exists a multitude of different medications—with a wide range of potencies, targeting a vast array of medical conditions—made up of varied combinations of cannabinoids, terpenes, and flavonoids.

Psilocybin, the primary ingredient found in mushrooms that produce psychoactive effects, in enjoying an increased share of popularity and renewed exploratory use.

It’s exciting that patients are starting to ask their pharmacist about psilocybin,” said Emily Kulpa, PharmD, an integrative health pharmacist and psychedelic medicine consultant based in Milwaukee, Wisconsin.

Although psychedelic mushrooms have been used for millennia, they gained popularity in the United States for recreational use during the 1960s and had spawned some academic interests as well. From 1960 to 1962, psilocybin, along with psychedelic relatives lysergic acid diethylamide (LSD) and mescaline, became the focus of a series of trials known as the Harvard Psilocybin Project. At the time, these drugs were legal. Criminalization of these drugs would later erupt in the following decade as safety concerns grew.

Fast-forward to the new millennium. Psilocybin sparked some interest in its potential analgesic effects in cluster headaches and migraines. Psilocybin agonizes the 5-hydroxytryptamine receptor and may interact with nociceptive and antinociceptive processing. The results from one 2016 retrospective study Googling the keywords “cluster headache discussion forums” and “migraine discussion forums” found that patients who self-treated themselves with psychedelic tryptamines such as psilocybin and LSD reportedly experienced a reduction in cluster frequency and severity.

Although these claims may warrant clinical study in pain management, research has focused on the role of psilocybin in mood disorders. Kulpa credits events in popular culturwith helping bring psilocybin into the mainstream. In the fall of 2019, Johns Hopkins announced the opening of the Center for Psychedelic & Consciousness Research, the first institution in the United States devoted exclusively to psychedelic research.

Indigenous to Thailand, Malaysia, Myanmar, and other regions of Southeast Asia, kratom (Mitragyna speciosa) belongs to the coffee family and also exhibits dose-dependent sedative and stimulatory effects. The plant is typically consumed in pill, capsular, or extract form, although some individuals brew dried or powdered leaves as a tea. Others may chew, smoke, or consume the leaves in food. However, because of kratom’s harmful adverse effects and abuse potential, the FDA warns individuals against using the substance.

Kratom contains mitragynine, an alkaloid bearing a tryptaminelike structure that exhibits µ- and ∂-opioid receptor agonist activity that results in dose-dependent stimulatory and analgesic effects. In lower doses, mitragynine produces stimulatory effects, whereas higher doses result in opioid-like activity. However, its metabolite, 7-α-hydroxymitragynine, exhibits significantly stronger µ-opioid receptor agonist behavior.

Although kratom is not an opioid, the CDC found an association between kratom use and overdose deaths, also involving opioid and nonopioid use, in the State Unintentional Drug Overdose Reporting System. Moreover, based on toxicology results, medical examiners or coroners determined kratom as the culprit in deaths in 11 states from July 2016 to June 2017 and 27 states during the last 6 months of 2017.

“There is no legitimate medical use for kratom in the [United States],” the Drug Enforcement Administration (DEA) wrote in a report on its website.8 On August 16, 2016, the DEA announced its intent to classify kratom as a Schedule I controlled substance, noting that the plant had been “abused for its ability to produce opioidlike effects” and “was often marketed as a legal alternative to controlled substances.”

Pharmacists should be aware of the substance so they can educate patients about the potential harms.

Varanasi believes the importance of cannabis in pain management will only continue to grow. “Preliminary evidence demonstrates cannabis’ ability to provide significant pain relief as well as [to help individuals] taper off opioids [particularly in the setting of addiction],” she said. “Though the research is inconclusive, patient anecdotes support the continued use of cannabis in pain management.”

In Oregon, the Oregon Psilocybin Program Initiative will appear on ballots in November 2020. “If passed, it would [be] the first state-sanctioned program for the administration of psilocybin services between a certified practitioner and a patient,” Varanasi said. “This would not only set the standard for other states but also support published studies reporting that a strong patient-practitioner relationship improves overall health outcomes.”

In the meantime, patients and practitioners alike will have wait to see how these and other psychedelics will alter integrative medicine and the world of health care.

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Once largely stigmatized, illicit substances are breaking into the field of pain management. 