Levetiracetam-induced rage and suicidality: Two case reports and review of literature

Background: Levetiracetam-induced rage is a rare neurobehavioral adverse effect of levetiracetam that is characterized by seething rage, uncontrollable anger, fits of fury, depression, violence, and suicidal tendencies. It occurs more in patients with prior mood or psychotic disturbances. No such case has been reported in Nigeria. Method: We report two cases of levetiracetam-induced rage. The first patient was a 29-year-old male with a 14-year history of intractable posttraumatic epilepsy. He was initially placed on sodium valproate and phenobarbitone and later had phenobarbitone replaced with levetiracetam. Within the first week of initiating levetiracetam, he became aggressive, bursted into fits of fury, and attacked his siblings. Levetiracetam was stopped, and the seething rage ceased only to reappear when it was reintroduced; hence, the complete withdrawal of levetiracetam. Naranjo probability score for adverse drug reaction was 8. Results: The second patient was a 23-year-old lady who developed seething rage and made several attempts to kill herself with a knife following addition of levetiracetam to the clonazepam and carbamazepine that she was taking for treatment-resistant epilepsy. Withdrawal and reintroduction of levetiracetam by the relatives led to cessation and reemergence, respectively, of the rage and suicidal tendencies. Naranjo score was 8. Levetiracetam was discontinued. Conclusion: Neuropsychiatric evaluation for prior mood or psychiatric disorders in those initiating levetiracetam therapy is suggested alongside monitoring for early features of levetiracetam-induced rage by both caregivers and physicians. This will help stem the morbidity and potential mortality associated with this life-threatening adverse drug reaction

Knowledge, attitude and practice of epilepsy among community residents in Enugu, South East Nigeria

AbstractPurposeThe understanding of the opinions of the Nigerian public about epilepsy and its treatment is relevant to the reduction of the large treatment gap that exists in management of the condition. The major aim of this study was to determine the knowledge and attitudes of urban dwellers to epilepsy and its treatment and to identify the gaps in knowledge that could pose as barriers in the treatment and care of epilepsy patients within the community.MethodThis cross-sectional and descriptive study was carried out in one of the districts of Enugu metropolis, Nigeria. Data collection was by means of a semi-structured validated questionnaire.ResultsThe mean score in knowledge was low, 48.1±18.8%; higher in females (50.6±18.6%, p=0.03 and those who had witnessed seizures in the past 49.7±18.8, p<0.01. On attitudes, 61.8% of the respondents accepted that it is right if sufferers married but most (93.2%) would not marry them and 87.2% would not allow them to have children or make a new acquaintance by working or playing with them (72.8%). There were no significant differences in the attitude scores of respondents with different levels of education.ConclusionThe level of knowledge of epilepsy in among urban dwellers in SE Nigeria is low and fraught with misconceptions and gaps. There were no significant differences in the attitude scores of respondents with different levels of education. There is a need for a multi-faceted educational interventions directed at improving the awareness and understanding of the condition by all segments of the society

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients

BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa. RESULTS: At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. CONCLUSIONS: NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible

Progress report on the first sub-Saharan trial of newer versus older antihypertensive drugs in native black patients

ABSTRACT: BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and [less than or equal to]2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure 65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had alpha-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. CONCLUSIONS: NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible.status: publishe

Heart rate variability on antihypertensive drugs in black patients living in sub-Saharan Africa

BACKGROUND: Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in blacks born and living in Africa. METHODS: In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30–69 years) with uncomplicated hypertension (140–179/90–109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. RESULTS: Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (− 2.2 beats/min). R patients had reduced total (− 0.13 ms²; p = 0.0038) and low-frequency power (− 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (− 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (− 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. CONCLUSION: In native black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate

Heart rate variability on antihypertensive drugs in Black patients living in sub-Saharan Africa

Background. Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in Blacks born and living in Africa. Methods. In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30-69 years) with uncomplicated hypertension (140-179/90-109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. Results. Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (- 2.2 beats/min). R patients had reduced total (- 0.13 ms²; p = 0.0038) and low-frequency power (- 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (- 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (- 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. Conclusion. In native Black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=iblo20status: publishe