Trends in the consumption and cost of antiepileptics in Morocco between 2008 and 2018.

INTRODUCTION: Epilepsy is one of the most common chronic neurological diseases. In Morocco, it is the second most common reason for consulting a neurologist. Its prevalence was estimated in Casablanca in 1998 at 1.1%. This study was carried out with the aim of evaluating, on the one hand, the consumption of antiepileptics and, on the other hand, the impact of their generic drugs on the pharmaceutical market between 2008 and 2018 in Morocco. MATERIALS AND METHODS: We used sales data for antiepileptic drugs collected from the Moroccan subsidiary of IQVIA, a multinational healthcare data science company, and we converted them into a defined daily dose (DDD/1000 inhabitants). RESULTS: The consumption of antiepileptic drugs increased from 442 to 641 DDD/1000 inhabitants between 2008 and 2018, all molecules combined, recording a 45% increase in the period studied. From an economic point of view, the calculation of the average cost of DDD, all molecules combined, gives an average cost of 2.42 dollars/DDD in 2018 versus 3.53 dollars/DDD in 2008 (1 dirham = 0.11 dollar), which corresponds to a decrease of -30%. This is due mainly to the introduction of generic drugs. CONCLUSION: These results show that while the average cost of a DDD has decreased, the consumption of antiepileptics has increased in Morocco over the years. Several events that have marked the drug market in Morocco have contributed to this trend, including the arrival on the market of several new molecules indicated for the treatment of epilepsy, the decrease in drug prices in 2014 and the policy of promoting generic drugs.

[Interictal psychosis of epilepsy]. / Les psychoses épileptiques interictales.

Interictal psychosis (IIP) refers to psychosis that occurs in clear consciousness in persons with epilepsy (PWE) with temporal onset not during or immediately following a seizure. The pooled prevalence estimate of psychosis in PWE is 5.6%. PWE and schizophrenia have very high mortality, and more than one in four persons with both disorders die between the age of 25 and 50years. IIP can manifest in brief or chronic forms. The chronic forms of IIP may closely resemble schizophrenia. However, some authors have described the typical presence of persecutory and religious delusions, sudden mood swings and the preservation of affect, as well as rarity of negative symptoms and catatonic states, but these differences remain controversial. Typically, IIP starts after many years of active temporal lobe epilepsy. Several epilepsy-related variables are considered pathogenically relevant in IIP including epilepsy type and seizure characteristics. Risk factors for developing IIP are family history of psychosis, learning disability, early age of onset of epilepsy, unilateral or bilateral hippocampal sclerosis, history of status epilepticus, history of febrile seizures, and poorly controlled temporal lobe epilepsy. In patients with epilepsy and psychosis, structural imaging studies have shown several relevant changes leading to conflicting findings. Altered neuronal plasticity and excitability have been described in epilepsy and psychotic disorders. Neuropathological data suggest that IIP are not the result of classic epileptic pathology of the temporal lobe. Forced normalization (FN) and alternating psychosis refer to patients with poorly controlled epilepsy (focal or generalized) who have had psychotic episodes associated with remission of their seizures and disappearance of epileptiform activity on their EEGs. FN mainly occurs in temporal lobe epilepsy when patients have frequent seizures that are abruptly terminated triggered by an antiepileptic drug, vagus nerve stimulation or epilepsy surgery. Treatment is based on withdrawal of the responsible drug, and by transient use of antipsychotics for acute symptomatic control on a case-by-case basis. FN is an entity whose pathophysiology remains uncertain. Antiepileptic drugs (AEDs) may sometimes induce psychotic symptoms and psychosis could be a direct effect of the AEDs. IIP has been reported more frequently following the initiation of zonisamide, topiramate, and levetiracetam when compared with other antiepileptic drugs. However, AEDs do not appear to be the only determinant of IIP. The management of IIP requires a multidisciplinary approach with early involvement of a liaison psychiatrist associated with a neurologist. IIP are underdiagnosed and mistreated. Existing recommendations are extrapolated from those established for the treatment of schizophrenia with some additional guidance from expert opinions. A two-step procedure, not necessarily consecutive, is suggested. The first step requires reevaluation of the antiepileptic treatment. The second step requires initiation of atypical neuroleptics. Antipsychotic drugs should be selected with consideration of the balance between pharmacological profiles, efficacy, and adverse effects. Regarding pharmacokinetic interactions, AEDs with inducing properties reduce the blood levels of all antipsychotics. It is important to consider implications of combining neuroleptics and AEDs with a similar spectrum of side effects. Regarding the duration of treatment, IIP episodes are more likely to be recurrent than in primary schizophrenia. In practice, atypical neuroleptics with few motor side effects such as risperidone can be used as first choice, given the low propensity for drug-drug interactions and the low seizure risk, with the added suggestion to start low and go slow. Clozapine could be prescribed in selected cases.

[Antiepileptic drugs administration by nasogastric tube in comatose patients]. / Modalités d'administration des antiépileptiques par sonde nasogastrique chez des patients comateux : étude des connaissances, attitudes et pratiques.

AIM: To evaluate the modalities of administration of antiepileptic drugs (AED) with nasogastric tube (NGT) by nurses and to draw up recommendations. METHODS: Our study consisted on investigating the modalities of administration of AED's with NGT by nurses during four months. We prepared 10 questions including demographic information. Participation was voluntary and anonymous. The questionnaire was distributed in seven intensive care departments after authorization of each head of the department. Thus, 45 nurses were included. RESULTS: Nurses sex ratio was 1.5 and mean age was 31 years (25 to 37 years). Among the nurses, 60% mentioned that the NGT were silicone made and 4% that they were PVC made. The mean duration before replacing the NGT was thought to be 5±3 days. Among the nurses, 91% affirmed to clear the NGT after each use. All the nurses had agreed that the solid form is the most commonly used pharmaceutical form in the NGT. AED were associated with the enteral feeding solution in 56%. The AED should be crushed before administration for 98% of the nurses even in case of polymedication. Among them, 62% recommended to crush all of the associated drugs together. Before introducing the AED into the NGT, 93% of the nurses reported mixing with tap water. We have noticed that 62% of nurses felt the need to improve their knowledge AED administration with NGT. CONCLUSION: To optimize AED therapy, modalities of administration by NGT in epileptic comatose patients should be enhanced.

[Epicutaneous patch testing in delayed drug hypersensitivity reactions induced by antiepileptic drugs]. / Place du patch-test dans le diagnostic des réactions d'hypersensibilités retardées induites par les antiépileptiques.

INTRODUCTION: Antiepileptic drugs are widely used and are associated with numerous side effects including skin eruptions. Epicutaneous tests have been used with variable success in skin drug reactions. The purpose of this study was to evaluate the profitability of epicutaneous tests in delayed hypersensitivity reactions induced by antiepileptic drugs. METHODS: We analyzed all cases of allergic skin reactions to antiepileptic drugs notified in regional pharmacovigilance center of Sfax (Tunisia) between June 1, 2014 and April 30, 2016. The imputation score, determined using the French imputation method, should be at least doubtful. Patch-tests were performed in accordance with the general Europen network on Drug Allergy/European Academy of Allergy and Clinical Immunology (ENDA/EAACI) guidelines. Patch-tests were read according to the generally accepted criteria of the International contact dermatitis research group (ICDRG). RESULTS: In our study, 20 patients were included, among which 23 events were observed. The drug involved in delayed hypersensitivity reactions was carbamazepine in 11 cases, phenobarbital in 10 cases and valproic acid in 4 cases. The clinical reactions caused by the drug were classified as maculopapular exanthema (11 cases), DRESS syndrome (6 cases), Stevens-Johnson syndrome (2 cases), fixed drug eruption (2 cases) and erythroderma (2 cases). Patch-tests were positive in 19 patients (95 %). Cross-reactivity between antiepileptic drugs was observed in 4 cases: between valproic acid and carbamazepine in 2 cases between valproic acid and phenobarbital in 1 case and between phenobarbital and carbamazepine in 1 case. CONCLUSION: In this study, patch testing was a safe and useful method in confirming the culprit drug in delayed hypersensitivity reactions induced by antiepileptic drugs.

[Management of neuropathic pain]. / Prise en charge de la douleur neuropathique.

Neuropathic pain is often underestimated and not adequately treated. The DN4 scale is very useful for its identification since it will benefit from pharmacological and non-pharmacological specific alternative care. The pathophysiological mechanisms involve the hyperexcitability of nociceptive pathways or decreased inhibitory descending controls that will be the target of pharmacological treatments. Frontline molecules are antidepressants (tricyclics and mixed serotonin and norepinephrine reuptake inhibitors) and antiepileptics (α2δ calcium channel inhibitors). However, these drugs will only have a partial efficacy on pain. The therapeutic strategy is based on reasonable goals, starting with a monotherapy adapted to the patient's symptoms and comorbidities and increased step by step. Patient compliance to contract is essential and requires clear and complete information. The impact on profession, social and family integration should rapidly be taken into account. In case of inefficiency, a change of the first-line treatment or an association could be considered. Some indications justify a specific therapy. Patients with resistant chronic pain should be sent to a specialized centre. New drugs are being studied and non-pharmacological support must be evaluated.