A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine / Estudo controlado, randomizado e duplo cego do uso de baixas doses de propranolol, nortriptilina e a combinação destas duas drogas no tratamento preventivo da migrânea

Few trials have evaluated combination of two or more drugs in the preventive treatment of migraine. In this study three therapeutic regimens were compared: (a) propranolol, at a dose of 40 mg per day, (b) nortriptyline, at a dose of 20 mg per day, and (c) the combination of these two drugs in these dosages. The groups were matched according to age, gender, and frequency of migraine attacks prior to treatment. The period of treatment was two months and the frequency and intensity of headache attacks of the 30 days pre-treatment period were compared with the frequency of headaches in the treatment period. Fourteen patients in groups A and B and sixteen patients in group C have completed the study. Treatment with propranolol, alone or in combination, was shown to be effective. Treatment with nortriptyline alone was not effective. All three therapeutic regimens were safe and side effects were minimal. The frequency of discontinuation of the study was the same in the 3 groups but no patient left the study due to adverse reactions. The combined therapy proved to be as safe as the monotherapy. Further studies evaluating this and other possible combinations of drugs in higher doses and for longer periods, should more clearly elucidate the role of combined therapy in the treatment of migraine.

Poucos ensaios clínicos têm avaliado o tratamento preventivo da migrânea através da combinação de drogas. Neste estudo, três regimes terapêuticos foram comparados: (a) popranolol, na dose de 40 mg por dia, (b) nortriptilina, na dose de 20 mg por dia e (c) combinação destas duas drogas nestas dosagens. Os grupos foram pareados de acordo com idade, sexo e freqüência de crises previamente ao tratamento. O período de tratamento foi de dois meses e a frequência e a intensidade das crises de cefaléia do período pré-tratamento foram comparadas com as do período de tratamento. Concluíram o estudo 14 pacientes do grupo A, 14 do grupo B e 16 do grupo C. Os tratamentos com propranolol, isolado ou em associação mostraram-se eficazes. O tratamento com nortriptilina isolada não se mostrou eficaz para a redução do número de dias com cefaléia. Todos os três regimes terapêuticos foram seguros e os efeitos colaterais foram mínimos. A freqüência de abandono do estudo foi a mesma nos 3 grupos e nenhum paciente abandonou o estudo devido a reações adversas. A terapia combinada mostrou-se tão segura quanto a monoterapia. Estudos futuros avaliando esta e outras possíveis combinações de drogas, em doses maiores e por períodos mais longos, deverão elucidar mais claramente o papel da terapia combinada no tratamento da migrânea.

La insulinoterapia intensificada más antineuríticos es superior a antineurítico puro en neuropatía diabética dolorosa / Intensified insulin therapy plus antineuritic medication is more effective than antineuritics alone in painful diabetic neuropathy

Background: The basis of the treatment of painful diabetic neuropathy is the use of drugs that block the transmission of pain (antineuritics) and a good metabolic control of underlying disease. Aim: To describe the outcomes of 17 type-2 diabetics with painful neuropathy, treated between 1988 and 2005 with symptomatic therapy plus intensified insulin. Material and methods: Review of medical records of 17 type-2 diabetic patients, aged 63±11 years and a duration of diabetes of 15±8 years. All patients received intensified insulin therapy with 0.35 units/kg of NPH insulin (2/3 before breakfast and 1/3 evening meal), plus capillary glucose measurements and regular insulin (with sliding-scale centered in ~0.1 units/kg) before the 3 main meals. All patients were also treated with gabapentin, nortriptyline or clomipramine. Pain was assessed using a visual analog score of 10 points. Results: After 1 year, glycosilated hemoglobin decreased from 10.0±1.4 percent to 7.7±1.2 percent (p~=0.003). Pain decreased from 10 to 5.1±3.3 at one month, 2.3±3.2 at six months, and 3.1±3.6 at 1 year (p <0.01). There was a direct statistical correlation between the reduction of HbA1C and pain decline (r =0.736; p =0.037). Pain scores were lower than those reported elsewhere for Pregabalin (n =76; p =0.05), Lamotrigine (n =27; p <0.0005), Topiramate (n =208; p <0.005), and Gabapentin (n =84; p <0.025). The lack of difference to Sodium Valproate (n =21; p =0.07) had borderline significance. Conclusions: The addition of intensified insulin therapy to the symptomatic treatment of painful neuropathy in type-2 diabetics, significantly enhanced the reduction of pain. The lowering of glycosilated hemoglobin was a significant predictor of success in pain reduction.

Métodos para abandono do tabagismo e tratamento da dependência da nicotina / Methods for smoking cessation and treatment of nicotine dependence

O tabagismo está relacionado a 30% das mortes por câncer. É fator de risco para desenvolver carcinomas do aparelho respiratório, esôfago, estômago, pâncreas, cérvix uterina, rim e bexiga. A nicotina induz tolerância e dependência pela ação nas vias dopaminérgicas centrais, levando às sensações de prazer e recompensa mediadas pelo sistema límbico. É estimulante do sistema nervoso central (SNC), aumenta o estado de alerta e reduz o apetite. A diminuição de 50% no consumo da nicotina pode desencadear sintomas de abstinência nos indivíduos dependentes: ansiedade, irritabilidade, distúrbios do sono, aumento do apetite, alterações cognitivas e fissura pelo cigarro. O aconselhamento médico é fundamental para o sucesso no abandono do fumo. A farmacoterapia da dependência de nicotina divide-se em: primeira linha (bupropiona e terapia de reposição da nicotina), e segunda linha (clonidina e nortriptilina). A bupropiona é um antidepressivo não-tricíclico que age inibindo a recaptação de dopamina, cujas contra-indicações são: epilepsia, distúrbios alimentares, hipertensão arterial não-controlada, abstinência recente do álcool e uso de inibidores da monoaminoxidase (MAO). A terapia de reposição de nicotina pode ser feita com adesivos e gomas de mascar. Os efeitos da acupuntura no abandono do fumo ainda não estão completamente esclarecidos. As estratégias de interrupção abrupta ou redução gradual do fumo têm a mesma probabilidade de sucesso.

Smoking is related to 30 percent of cancer deaths. It is a risk factor for respiratory tract, esophagus, stomach, pancreas, uterine cervix, kidney and bladder carcinomas. Nicotine induces tolerance and addiction by acting on the central dopaminergic pathways, thus leading to pleasure and reward sensations within the limbic system. It stimulates the central nervous system (CNS), enhances alertness and reduces the appetite. A 50 percent reduction of nicotine consumption may trigger withdrawal symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy) and second-line (clonidine and nortriptyline) drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinence and current therapy with MAO inhibitors. Nicotine replacement therapy can be done with patches or gums. Counseling groups and behavioral interventions are efficacious. The effects of acupuncture on smoking cessation are not fully elucidated. Prompt smoking cessation or gradual reduction strategies have similar success rates.

Hipoestesia emocional induzida pelos Inibidores da Recaptaçäo da Serotonina (IRS) - Efeitos antipreocupaçäo, apatia e incapacidade de chorar / Emotional hypoesthesia SRI-induced - Antiworry effect, apathy and inability to cry

Os IRS podem ter importante propriedades além dos efeitos antidepressivos e antiobsessivos. Relatos anedóticos sugerem que podem funcionar como agentes "antipreocupaçäo" diminuindo a "preocupaçäo ansiosa" que impede o indivíduo de obter distanciamento emocional de fontes de estresse. Esta açäo antipreocupaçäo pode causar problemas, especialmente quando mais acentuada, por exemplo: incapacidade de chorar, indiferença e apatia. Denominamos "hipoestesia emocional" tanto a açäo terapêutica (antipreocupaçäo) quantos os efeitos colaterais (incapacidade de chorar, indiferença e apatia) induzidos pelos IRS. Relatamos 6 casos de "hipoestesia emocional" em pacientes que tomaram fluoxetina e paroxetina. Esses efeitos colaterais remitiram com a reduçäo da dose ou com a retirada do IRS. O mecanismo pelo qual o IRS produz a "hipoestesia emocional" pode ser pelo agonismo serotoninérgico que acarreta uma inibiçäo do sistema dopaminérgico. Se este efeito modulador indireto ocorre no sistema dopaminérgico mesolímbico/mesocortical produz uma disfunçäo do lobo frontal que pode ser tratada com psicoestimulantes; se ocorre no trato nigro-estriatal, produz efeitos colaterais extrapiramidais tais como a acinesia. Agentes anticolinérgicos, teoricamente, poderiam tratar a apatia e a indiferença devido à acinesia induzida pelos IRS. O maior conhecimento sobre a apatia, indiferença e incapacidade de chorar induzidas pelos IRS pode otimizar os resultados terapêuticos, por ex., pela reduçäo de doses, e consequentemente melhor adesäo dos pacientes ao tratamento

The treatment of fetishism and socially inappropriate sexual behavior in a young male with dull normal intelligence.

A young adult male with dull normal intelligence who had a fetish to female undergarments and was engaging in socially inappropriate sexual behavior was evaluated and treated in a multimodal treatment approach. Mild and diffuse encephalopathies were noted through EEG recordings. No definite epileptiform abnormalities or focal supratentorial lesions were seen and the pattern was consistent with patients with post-encephalitis. Treatment of this patient involved the use of anti-androgen and antianxiety pharmacotherapy along with counseling to provide basic sex education and specific education for socially accepted sexual behavior. Follow-up evaluation several yrs later indicated good treatment results. This case illustrates potential sources of sexually deviant behavior and treatment options. Promising new drug treatments are available which act as sexuoerotic tranquilizers as well as treatments for underlying or concomitant psychiatric disorders. In this case, however, family dynamics and poor sex education seemed to account for most of this patient's difficulties. Counseling and psychoeducation proved to be quite effective in resolving problematic behavior.