INTRODUCTION:

Migraine is a common and often disabilitating neurological condition characterized by primary recurrent headaches lasting 4 to 72 h with at least two of the following pain characteristics: unilateral, pulsating, moderate or severe intensity¹. The pain is generally made worse by physical activity. Migraines typically present with self-limited, recurrent severe headache associated with autonomic symptoms. The term classical migraine and nonclassical migraine is now replaced by migraine with aura and migraine without aura. About 15–30% of people with migraines experience migraines with an aura and those who have migraines with aura also frequently have migraines without aura. The severity of the pain, duration of the headache, and frequency of attacks are variable. A migraine lasting longer than 72 hours is termed status migrainosus.

Up to one-third of people have an aura: typically a short period of visual disturbances which signals that the headache will soon occur. Occasionally, an aura can occur with little or no headache following it.

The word migraine comes from the Greek “hemicranias” and historically was used to describe unilateral headaches with associated symptoms.

According to the World Health Organisation, migraine is ranked 19^th among all diseases causing disability and is the 12^th leading cause of years lived with disability among females of all ages worldwide². Migraines are believed to be due to a mixture of environmental and genetic factors. About two-third of cases run in families. Changing hormone levels may also play a role, as migraines affect slightly more in boys than girls before puberty.

Based on the International Headache Society (IHS) guidelines, migraine is classified as episodic (EM) or chronic (CM), with CM defined having 15 or more headache days of which at least three months (IHS Classification ICHD-III)¹.In addition, health care costs and productivity loss at work were larger in patients with CM than those with EM³.

Prevalence is highest during an individual’s peak productivity years, between the ages of 25 and 55, where it has significant impact on daily life with substantial functional impairment that includes both physical and emotional ramifications. More than half of people with migraine require bed rest to manage their pain, leading to work/school absenteeism. Estimates of the burden of migraine suggest that the average impact of migraine on worker productivity is approximately a loss of four workdays per year and 10 days of reduced productivity¹. Recurrence of headache within two days following successful termination of migraine is reportedly as high as 50%, and up to 10% of patients treated in emergency departments will return for this ‘rebound’ headache.

Migraine treatment may be either prophylactic (preventive) or abortive (rescue). Preventive treatments can be sub-divided into non-drug treatments, and treatment with medication. Non-drug treatment, when possible, is preferable because of the high incidence of unpleasant or debilitating side-effects that occur with migraine preventive drugs. Prophylactic treatment is used in order to reduce the frequency of migraine attacks. It can improve the quality of life of the patients and reduce the burden of migraine⁴. Because of frequent unpleasant and sometimes debilitating side effects, preventive drugs are only prescribed for those migraineurs whose quality of life is significantly adversely affected. The most commonly prescribed drugs for migraine prevention are beta-blockers, antidepressants, anticonvulsants and calcium channel blockers.

The aim of the study is to evaluate comparative effectiveness of Propranolol vs Flunarizine in the prophylactic treatment of migraine

Objectives include:

1 The effectiveness of the two antimigraine drugs in reducing the symptoms of migraine.

2 To assess the Quality of life in patients suffering from migraine.

3 Recurrence rate of migraine during study period.

4 To assess the risk factors associated with migraine.

5 To assess the side effects of the drugs

MATERIALS AND METHODS:

STUDY DESIGN:

Prospective observational study.

STUDY POPULATION:

Patients diagnosed with migraine.

INCLUSION CRITERIA:

· Patients with migraine.

· Prescription with either flunarizine (10 mg) or propranolol (40 mg).

· OP patients.

· Both male and female patients.

· Age group >16 years

· Those who give consent voluntarily to participate in the study.

EXCLUSION CRITERIA:

· Patients not willing to participate.

· Patient who take more than one medication for migraine prophylaxis.

· Patient who overuse pain medication

STUDY SITE:

Neurology department of Pushpagiri Medical College Hospital, Thiruvalla, kerala.

SAMPLE SIZE:

70 patients diagnosed with migraine, 35 treated with propranolol and remaining 35 with flunarizine.

EQUATION:

(Z_α +Z_β)² [ P₁( 1-P₁) + P (1-P₂)]

N = ––––––––––––––––––––––––––––

(P₁ – P₂)²

α = Type I error (fixed at 5 % level)

β = Power (fixed at 80 % level)

P₁= Proportion having clinical response in propranolol arm

P₂= Proportion having clinical response in flunarizine arm.

STUDY PERIOD:

6 months, From January 2018- June 2018

ETHICAL CONSIDERATION:

The institutional ethics committee clearance was obtained (IEC No is PCP/E1/01A/03/ 2018), after that started the study. Informed consent was obtained from all patients who met the inclusion criteria were enrolled for the study.

RESULT AND DISCUSSION:

Effectiveness:

Fig 1: Effectiveness of medication based on severity of migraine patients

In the study population, the average severity score of the patients with propranolol were decreased from 8.1 to 1.5, indicating the effectiveness of propranolol on severity of migraine patients. Here the P value was found to be ˂ 0.0001 indicating that the effectiveness of medication on severity was significant.

Fig 1.2 Effectiveness of medication based on frequency of migraine patients

In the study population, average frequency score of the patients with propranolol were decreased from 10.74 to 1.77, indicating the effectiveness of propranolol on frequency of migraine patients. Here the P value was found to be ˂0.0001 indicating that the effectiveness of medication on frequency was significant.

Fig 1.3 Effectiveness of medication based on duration of migraine patients

In the study population, average duration score of the patients with propranolol were decreased from 9.2 to 2.37 and patients with flunarizine decreased from 8.2 to 1.43 and the mean difference were almost equal indicating that both propranolol and flunarizine were equaly effective on duration of migraine patients. Here the P value was found to be ˂0.0001 indicating that the effectiveness of medication on duration was significant.

RISK FACTORS OF MIGRAINE:

Table 1: Distribution of migraine in patients based on triggering factors

Triggering factors	frequency	percentage (%)
STRESS	19	27.1
MISSED MEALS	13	18.6
CHANGE IN CLIMATE	17	24.3
TRAVEL	9	12.9
CHANGE IN SLEEP PATTERN.	12	17.1

From table 1, it was clear that stress and climatic changes can trigger migraine in most of the study population.

RECURRENCE RATE OF MIGRAINE DURING STUDY PERIOD:

Table 2: Distribution of patients based on recurrence rate

Recurrence rate	propranolol	flunarizine
RECURRENCE	17.1	11.4
NO RECURRENCE	82.9	88.6

From table 2 shows that majority of the study population reported no recurrence of migraine. Recurrence rate was only 14.2% in the study population. Recurrence rate was higher with propranolol use than with flunarizine by 5% only.

QUALITY OF LIFE ANALYSIS:

Fig 2: Improvement of quality of life on therapy

From fig 2, it was clear that difference in QOL based on therapy was significant, in which case improvement was greater on propranolol therapy in case of bodily pain, vitality and social functioning.

Fig 3: Distribution of patients based on the occurrence of ADR

Out of 70 patients, commonly observed ADR was sedation (17.1%) and weight gain (5.7%) associated by the use of flunarizine and for Propranolol was sedation (2.9%) and hypotension (5.7%). By Naranjo algorithm, 84.3% were doubtful ADR and 15.7% was possible chance of ADR.

CONCLUSION:

Propranolol was found to be significantly more efficacious in this study. At the same time recurrence rate of migraine was slightly higher in patients on propranolol therapy. Quality of life of both treatments was similar except for vitality, mental health and social functioning. There was a greater difference achieved through propranolol therapy. As such, it may be concluded propranolol can be considered a safe alternative to flunarizine in the therapy of migraine.

Quality of Life assessment showed a significant fall in both physical and mental component scores upon contracting migraine and also causes considerable disability. These points to the fact that even headache must not be treated lightly. Control of risk factors such skipping meals, travelling, stress and non pharmacological treatment is very important even for an acute treatment. Seeking medical advice is necessary to avoid complications by undertaking suitable prophylactic therapy.

ACKNOWLEDGEMENTS:

I would like to thank Dr Byju P, Neurologist, Pushpagiri Medical College Hospital, Thiruvalla for his immense support and guidance for the success of the thesis work and also all the members of Pushpagiri College of Pharmacy.

REFERENCES:

1. Sally Mannix, Anne Skalicky, Dawn C.Buse, Pooja Desai, Sandhya Sapra, Brian Ortmeier, Katherine Widnell and Asha Hareendran. Measuring the impact of migraine for evaluating outcomes of preventive treatments for migraine headaches. Health and Quality Of Life Outcomes (2016)14:143

2. Munvar Miya Shaik, Norul Badriah Hassan, Huay Lin Tan, and Siew Hua Gan. Quality of Life and Migraine Disabilty among Female Migraine Patients in a tertiary Hospital in Malaysia. Biomed Research International (2015)52.3717

3. Sun-Young Kim and Sung-PA Park. The role of headache chronicity among predictors contributing to quality of life in patients with migraine: a hospital- based study. The Journal of Headache and Pain(2014),15:68

4. Renan B Domingues, Andre L Pirajada Silva, Simone A. Domingues, Camila Catherine H. Aquino, Gustavo W. Kuster. A double- blind randomized controlled trail of low doses of propranolol, nortriptyline, and the combination of propranolol and nortryptiline for the preventive treatment of migraine. Arq Neuropsiquiatr (2009); 67(4):973-977.

5 Aijie He, DehuaSong, Lei Zhang and Chen Li. Unveiling the relative efficacy, safety and tolerability of prophylactic medications for migraine: pairwise and network-meta analysis. The Journal of Headache and Pain 2017;18:26

6 Sulmaz Ghahramani, Negin Hadi, Abdolhamid Shariat, Zahra Memar, Ali Montazeri. Quality of Life of Migraine Patients Treated With Combined Propranolol and Topiramate. SMEJ. 2014; 15(4): e23277.

7 Ghasami k and Mohammad Beigi A. Comparison of treatment effect of sodium valproate, propranolol and tricyclic antideppresant in migraine. Pak. J. Biol. Sci. 2009; 12 (15):1098-1101.

8 Chandan Raybarman. The efficacy of combined low-doses of propranolol and flunarizine in episodic migraine . East J Med. 2016; 21(2): 75-78.

Received on 27.05.2019 Modified on 25.06.2019

Research J. Pharm. and Tech 2020; 13(5): 2159-2162.

DOI: 10.5958/0974-360X.2020.00388.1