Protocol synopsis

Title of study:

A prospective, open-label, multicentre, non-comparative, post marketing observational study evaluating effectiveness and tolerability of Carbamazepine (Tegrital®) as monotherapy in treatment naïve patients with generalized tonic-clonic seizures in routine clinical practice in India.

Purpose and rationale:

Epilepsy is the most common serious neurological disorder and is one of the world’s most prevalent non-communicable diseases. It is estimated that the condition affects approximately 50 million people, around 40 million of them living in developing countries¹. The incidence of epilepsy in low-income countries may be as high as 190 per 100 000 people². Consequently, in the context of the large and rapidly increasing populations in these countries, epilepsy is a significant health and socioeconomic burden requiring urgent attention^{3 4}.

 In 1990, the UK National General Practice Study of newly diagnosed epilepsy found that of 564 incident cases, 29% had primary and 28% secondary GTCS.⁵ In 1993, Hauser et al. reporting on the Rochester study for the years 1935–1984 found that secondarily generalized seizures and GTCS constituted figures of 15 and 10, respectively, of their total age-adjusted incidence of 44 per 100,000 patient-years.⁶ Murthy et al. in a hospital-based cohort of 2531 patients, found that 162 (6.4%) had idiopathic generalized epilepsies (IGE), and 503 (19.9%) were unclassified.⁷ The SANAD A and B studies with a total of 2437 patients, 559 (23%) had either generalized (excluding childhood absence epilepsy) or unclassified seizures. ⁸

Sridharan et al. in 1999 projected number of people with epilepsy in India to be 5.5 million by the year 2001 and based on the incidence of epilepsy, the number of new cases of epilepsy each year to be close to half a million, the number of people with epilepsy in rural areas was projected to be around 4.1 million by the year 2001.⁹

 Antiepileptic drugs (AEDs) are the mainstay of the treatment of epilepsy, and although their number has expanded exponentially, current principles governing drug therapy are in many ways similar to those established a century ago.¹⁰ Because AED therapy is typically maintained for several years and often for life, particularly in adults, a decision to initiate treatment has far-reaching consequences and needs to be based on careful risk-benefit analyses.^{11 12}

Recently released NICE 2012 guidelines on the diagnosis and management of the epilepsies in adults and children in primary and secondary care have placed Carbamazepine as first-line treatment in children, young people and adults with newly diagnosed generalised tonic clonic seizures.¹³

Carbamazepine is a dibenzazepine derivative, its spectrum of activity embraces: partial seizures (simple and complex) with and without secondary generalization; generalized tonic-clonic seizures, as well as combinations of these types of seizures. Carbamazepine stabilizes hyperexcited nerve membranes, inhibits repetitive neuronal discharges, and reduces synaptic propagation of excitatory impulses. The prevention of repetitive firing of sodium-dependent action potentials in depolarized neurons via use- and voltage-dependent blockade of sodium channels may be its main mechanism of action. Whereas reduction of glutamate release and stabilization of neuronal membranes may account mainly for the antiepileptic effects, the depressant effect on dopamine and noradrenaline turnover could be responsible for the antimanic properties of carbamazepine

Carbamazepine is available as Tegrital® in India and is indicated for the treatment of partial seizures and generalized tonic-clonic seizures, in adults and in children. Although there is ample amount of clinical data highlighting the safety and efficacy of carbamazepine, but there is dearth of such data in the Indian scenario. This current study is designed to analyze the extended effectiveness and tolerability of Tegrital® (Carbamazepine) in treatment of children and adults with newly diagnosed generalized tonic-clonic seizures in Indian population.