Eficácia e segurança de Duloxetina comparado a outros antidepressivos disponíveis no SUS para o tratamento de depressão maior: revisão rápida de evidências / Effectiveness and safety of Duloxetine compared to other antidepressant agents available in Brazilian Public Health for treatment of major depression: rapid response review of evidence

Tecnologia: Duloxetina e outros antidepressivos disponíveis no Sistema Único de Saúde (amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona). Indicação: Tratamento do primeiro episódio depressivo no transtorno de depressão maior em adultos. Pergunta: A duloxetina é mais eficaz e tolerável que a amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona para o tratamento do primeiro episódio de depressão maior em adultos? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada 1 revisão sistemática, que atendia aos critérios de inclusão. Conclusão: Os antidepressivos, comparados ao placebo, tinham maior taxa de resposta, taxa de remissão e taxa de descontinuação devido a efeitos colaterais, no tratamento de curto prazo. Duloxetina tinha taxa de resposta similar a amitriptilina, clomipramina, fluoxetina e bupropiona. Duloxetina e amitriptilina tinham maior taxa de remissão que fluoxetina. Comparando-se as taxas de abandono de tratamento devido a efeitos colaterais, clomipramina era menos seguro, amitriptilina, bupropiona e duloxetina eram parecidos entre si, e fluoxetina era o antidepressivo mais seguro

Technology: Duloxetine and other antidepressants available in the Brazilian Public Health System (amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion). Indication: Treatment of the first depressive episode in adult major depressive disorder. Question: Is duloxetine more effective and tolerable than amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion for the treatment of first episode of major depression in adults? Methods: Rapid response review of evidence (overview) from systematic reviews, with a bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Methodological Quality Assessment of Systematic Reviews). Results: One systematic review was selected, which met the inclusion criteria. Conclusion: In short-term treatment, antidepressants, compared to placebo, had a higher rate of response, rate of remission and rate drop-out due to side effects. Duloxetine had a similar response rate to amitriptyline, clomipramine, fluoxetine and bupropion. Duloxetine and amitriptyline had higher remission rates than fluoxetine. Comparing rates of dropout due to side effects, clomipramine had the worst rates, amitriptyline, bupropion, and duloxetine were similar to each other, and fluoxetine had the better rates

Lisdexanfetamina comparada a Metilfenidato ou antidepressivos no tratamento de TDAH em crianças e adolescentes: revisão rápida de evidências / Lisdexamfetamine compared to Methylphenidate or antidepressants for treatment of ADHD: rapid response review of evidence

Lisdexanfetamina e drogas disponíveis no SUS (metilfenidato, bupropiona, amitriptilina, clomipramina, nortriptilina). Indicação: Transtorno do Déficit de Atenção e Hiperatividade (TDAH) em crianças e adolescentes. Pergunta: Lisdexanfetamina é eficaz e segura para melhoria de sintomática, comparada ao placebo e medicações disponíveis no SUS, no tratamento de crianças e adolescentes com TDAH? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews). Resultados: Foram selecionadas 3 revisões sistemáticas, que atenderam aos critérios de inclusão. Conclusão: Lisdexanfetamina e metilfenidato são mais eficazes que placebo, e similares entre si, para reduzir sintomas em escalas de avaliação. Lisdexanfetamina e metilfenidato têm risco similar ao placebo de abandono do tratamento devido a efeitos adversos. Bupropiona não é mais eficaz que placebo para alívio sintomático. Lisdexanfetamina tem efeitos adversos de redução do apetite e insônia/ dificuldades do sono. Não foram encontradas evidências na literatura sobre os efeitos terapêuticos de amitriptilina, clomipramina e nortriptilina no tratamento de crianças e adolescentes com TDAH

Lisdexamfetamine and drugs available in the Brazilian Public Health System (BPHS) (methylphenidate, bupropion, amitriptyline, clomipramine, nortriptyline, bupropion). Indication: Children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Question: Lisdexamfetamine is effective and safe for symptomatic improvement, compared to placebo and drugs available in the BPHS, for treatment of children and adolescents with ADHD? Methods: Rapid response review of evidence (overview) of systematic reviews, with bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews). Results: 3 systematic reviews met the inclusion criteria and were selected. Conclusion: Lisdexamfetamine and methylphenidate are more effective than placebo, and similar to each other, to reduce symptoms on rating scales. Lisdexamfetamine and methylphenidate are not different from placebo in the risk of treatment discontinuation due to adverse effects. Bupropion is no more effective than placebo for symptomatic relief. Lisdexamfetamine has adverse effects of decreased appetite and insomnia/sleep troubles. No evidence was found in the literature about therapeutic effects of amitriptyline, clomipramine and nortriptyline for treatment of children and adolescents with ADHD

Nortriptyline, a tricyclic antidepressant, inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells

We demonstrated the effect of nortriptyline, a tricyclic antidepressant drug and serotonin reuptake inhibitor, on voltage-dependent K⁺ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Nortriptyline inhibited Kv currents in a concentration-dependent manner, with an apparent IC₅₀ value of 2.86±0.52 µM and a Hill coefficient of 0.77±0.1. Although application of nortriptyline did not change the activation curve, nortriptyline shifted the inactivation current toward a more negative potential. Application of train pulses (1 or 2 Hz) did not change the nortriptyline-induced Kv channel inhibition, suggesting that the effects of nortiprtyline were not use-dependent. Preincubation with the Kv1.5 and Kv2.1/2.2 inhibitors, DPO-1 and guangxitoxin did not affect nortriptyline inhibition of Kv channels. From these results, we concluded that nortriptyline inhibited Kv channels in a concentration-dependent and state-independent manner independently of serotonin reuptake.

Recent Updates on Chemotherapy-Induced Peripheral Neuropathy / 대한내과학회지

Chemotherapy induced peripheral neuropathy (CIPN) could debilitate the quality of life in the patients with cancer. According to the severity of CIPN, the modification of dosage of chemotherapeutic agents and switch to other drugs can be unavoidable. Platinum such as cisplatin and oxalipatin, vinka alkaloids, bortezomib, and taxane can cause CIPN. The characteristics and severity of CIPN depends on the dosages, duration of exposure of chemotherapeutic agents, comcomittant illness or other drugs affecting on peripheral nervous system and the methods of assessment for CIPN. The symptoms may last for several months or permanently even after quitting chemotherapy. Typically it distributed bilaterally and starts from the distal part of extremities and is presented progressively in stocking and glove pattern. Sensory nerve is more involved rather than motor nerve and amplitude of sensory nerve conduction is observed in CIPN. Prevention for CIPN is not effective at present. Tricyclic antidepressant including amitriptyline or nortriptyline and gabapentine have been tried in the practice for the management of CIPN despite of the lack of significant evidence through clinical trials. Recently duloxetine has been reported to decrease pain in the patients with CIPN compared with the patients with placebo (p = 0.03).

Eficacia y seguridad del uso de medicamentos para la cesación de la adicción al tabaco: revisión de guías de práctica clínica / Efficacy and safety of medication use for the cessation of tobacco addiction: Are view of Clinical Practice Guidelines

Objetivo Revisar la eficacia y seguridad de medicamentos para cesación del tabaquismo en el contexto de construcción de guías de práctica clínica (GPC). Métodos Revisión sistemática de GPC para adaptación mediante ADAPTE. Los desenlaces fueron cesación ≥6 meses y seguridad de las intervenciones. Las GPC se calificaron por pares con DELBI. Se extrajeron resultados de estudios agregativos incluidos en las guías seleccionadas. Resultados Los fármacos duplican la cesación comparados con placebo (tasas de 25,0 % hasta 27,0 % al combinarse con consejería). Los mayores incrementos en cesación se obtienen con ansiolíticos y antidepresivos (8,7% a 19,4%), y los menores con terapia de reemplazo nicotínico -TRN- (5,2% a 12,9%). La nortriptilina tiene eficacia similar al bupropion (aproximadamente 10,0 %). Con limitadas excepciones (parche e inhalador, tabletas y bupropion), las combinaciones de medicamentos no incrementan la abstinencia. Conclusiones TRN, vareniclina, bupropion y nortriptilina son eficaces para dejar de fumar. Las combinaciones de medicamentos requieren más evidencia y deberían restringirse a personas con alta dependencia o con falla terapéutica inicial. Serían deseables análisis de costo-efectividad para valorar implementación de programas en países en desarrollo.

Objective To review the efficacy and safety of pharmacotherapy for smoking cessation in the context of clinical practice guidelines (CPG). Methods A systematic review of CPGs was conducted, aimed at adapting recommendations for Colombia following the ADAPTE methodology. Outcomes comprised 6-months or higher smoking cessation rates and intervention safety. CPGs were peer-assessed based on DELBI. Results from aggregative studies included in selected CPGs were obtained. Results Pharmacotherapy doubles smoking cessation rates as compared with placebos (rates @25% and up to 27 % when combined with counseling). The highest efficacy was observed for ansyolitic and antidepressive drugs (8.7 % to 19.4 %), and the lowest for nicotine replacement therapy -NRT- (5.2 % to 12.9 %). Nortriptiline shows an efficacy similar to that of bupropion (@10%). With limited exceptions, combined pharmacotherapy for smoking cessation has shown no significant increase in cessation rates. Conclusions NRT, varenicline, bupropion and nortriptiline are effective treatments for smoking cessation. Combination of drugs deserves further clinical evidence and should be restricted to highly dependent smokers or initial therapeutic failure. Cost-effectiveness analyses might help to introduce smoking cessation programs in low and middle income countries.

Chemotherapy induced peripheral neuropathic pain / 대한마취과학회지

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious complications associated with anticancer drugs. CIPN leads to a lower quality of life and dysfunction of the sensory, motor, and autonomic systems, and often causes patients to discontinue chemotherapy. It is usually misdiagnosed and undertreated due to a lack of consensus and unclear pathophysiology, for which many mechanisms have been suggested, including mitochondrial dysfunction, various pain mediators, abnormal spontaneous discharge in A and C fibers, and others. To date, no agents have been shown to effectively prevent CIPN, leading to debate as to the standard protocol. Duloxetine has demonstrated a moderate therapeutic effect against CIPN. Although tricyclic antidepressants (such as nortriptyline or desipramine), gabapentin, and a topical gel containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg) showed inconclusive results in CIPN trials, these agents are currently considered the best options for CIPN treatment. Therefore, further studies on the pathophysiology and treatment of CIPN are needed.

The pharmacological management of neuropathic pain

Neuropathic pain has recently been defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". Neuropathic pain is a debilitating chronic condition that remains very difficult to treat and challenging to manage. Tricyclic antidepressants (amitryptiline, nortriptyline, imipramine), selective serotonin and norepinephrine reuptake inhibitors (duloxetine, venlafaxine), anticonvulsants (gabapentin, pregabalin), and 5% lidocaine patches have demonstrated efficacy in neuropathic pain and are recommended as first-line medications. In patients who fail to respond to these first-line medications alone and/or in combination, opioid analgesics or tramadol can be used as a second-line treatment alone or in combination with one of the first-line medications. Opioid analgesics and tramadol can also be considered for first-line use in selected clinical circumstances. Other pharmacological therapeutic options include selective serotonin reuptake inhibitors, antiepileptic drugs (levetiracetam, lacosamide, lamotrigine, valproic acid), cannabinoids, high concentration capsaicin patch, and botulinum toxin A. Medication selection should be individualized, with side effects taken into consideration as well as potential beneficial or deleterious effects on comorbidities, and whether or not prompt onset of pain relief is necessary.

A real-life study of the effectiveness of different pharmacological approaches to the treatment of smoking cessation: re-discussing the predictors of success

OBJECTIVE: To evaluate the effectiveness of nicotine replacement therapy (NRT), bupropion, nortriptyline and combination therapy and describe factors associated with treatment success. INTRODUCTION: Clinical trials clearly demonstrate the efficacy of pharmacotherapy in smoking cessation. However, it is only after its use in real-life settings that clinical effectiveness and limitations of a treatment are fully known. METHODS: Patients attended a four-session cognitive-behavioral program and received medicines free of charge. Abstinence from smoking was assessed at each visit. RESULTS: A total of 868 smokers (68.8 percent women) were included. Their mean age was 49.6 years; the amount smoked was 25 cigarettes/day and the Fagerströ m Score was 6.6. Abstinence rates after 6 months and 1 year were 36.5 percent and 33.6 percent. In univariate analysis, male gender, age (>50), higher number of cigarettes smoked, cardiovascular comorbidities, longer interval from the last cigarette and combined treatment of nortriptyline plus NRT were predictive of abstinence, while neuropsychiatric comorbidities and the answer ''yes'' to the question ''Do you smoke more often during the first hours after waking'' were correlated with failure. In a multivariate model, predictors of abstinence were neuropsychiatric comorbidities, the answer ''yes'' to the question ''Do you smoke more often during the first hours after waking'' and combined treatment of nortriptyline plus NRT. Male gender and a longer period from the last cigarette were correlated with lower abstinence rate. CONCLUSION: Satisfactory success rates were obtained in a teaching hospital. Factors such as age, daily cigarette consumption, number of pack-years and dependency score were not reliable markers of abstinence. The combination nortriptyline+NRT was independently associated with higher abstinence rates.

[Doxepin is more effective than nortriptyline and placebo for the treatment of diarrhea-predominant irritable bowel syndrome: a randomized triple-blind placebo-controlled trial]

The current treatment of IBS is often unsatisfactory and frustrating. Several controlled trials have demonstrated benefits of tricyclic antidepressants for irritable bowel syndrome, especially when pain is a prominent symptom but the efficacy of antidepressants in irritable bowel syndrome is controversial. The aim of this study was to compare the effect of doxepin and nortriptyline on diarrhea-predominant irritable bowel syndrome. Seventy-five patients with IBS according to Rome III criteria were treated for two months. The patients were randomly assigned to one of three groups treated with doxepin, nortriptyline or placebo. Subjects were assessed clinically one month and two months after treatment. The symptoms and adverse effects of the drugs were recorded in the questionnaire. The total score was considered as the number of the symptoms for each patient, which ranged between zero and six. Improvements in abdominal pain and bloating in the doxepin group were significantly higher than the nortriptyline or the placebo groups [P=0.001 and P=0.012, respectively]. However, improvement in diarrhea in patients on nortriptyline was significantly higher than the other groups [P=0.018]. The average improvement of symptoms in the patients after two months of treatment in doxepin, nortriptyline and placebo groups, respectively were 2.56, 2 and 0.6 [P<0.05]. Both doxepin and nortriptyline are effective for the treatment of diarrhea-predominant irritable bowel syndrome in a period of two months but doxepin seems to be more efficacious than nortriptyline in this regard. However, larger comparative trials are suggested

Conduta na dor e prurido vulvar / Pain and pruritus vulvae management

Prurido e dor são as principais manifestações clínicas das doenças vulvares. Estes sintomas podem estar associados a processos inflamatórios, imunológicos, distúrbios metabólicos e neoplasias. Na dúvida, é sempre recomendável o estudo histopatológico. Quando não há definição etiológica, várias opções terapêuticas estão disponíveis: cremes tópicos, fármacos sistêmicos, operações de dessensibilização nervosa da vulva. A conduta terapêutica deve ser individualizada quando não há etiologia definida. São escassos os trabalhos científicos, com metodologia adequada, que abordam o tema. Portanto, anamnese e exame físico cuidadosos irão definir a melhor abordagem terapêutica

Pruritus and pain are common manifestations of vulvae diseases. The symptoms can be associated with inflammatory, immunologic, metabolic or neoplastic diseases. Undoubtedly, the histopathological exam is always recommended. When there is no etiologic definition, many therapeutic options are available: creams, systemic drugs, and surgical neural desensitization of the vulvae. When there is no precise etiology, therapeutical approach must be individualized. Scientific studies, with good methodology, are rare. Therefore, careful anamnesis and physical exam will point to the best therapeutical approach

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.

Quetiapine for the prevention of migraine refractory to the combination of atenolol + nortriptyline + flunarizine: an open pilot study / Quetiapina para a prevenção da migrânea refratária à combinação de atenolol + nortriptilina + flunarizina: estudo piloto aberto

BACKGROUND: Migraine is a prevalent neurological disorder. Although prevention is the mainstream treatment, some patients are refractory to standard therapies. AIM: To evaluate the use of quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination atenolol + nortriptyline + flunarizine. METHOD: Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II) and headache attacks on less than 15 days per month not overusing symptomatic medications were studied. The main inclusion criterion was the lack of response (<50 percent reduction in attack frequency) after ten weeks to the combination of atenolol (60 mg/day) + nortriptyline (25 mg/day) + flunarizine (3 mg/day). The patients started on QTP as the sole treatment in a single daily dose of 25 mg, titrated to 75 mg. After ten weeks, headache frequency, consumption of rescue medications and adverse events were analyzed. RESULTS: Twenty nine patients completed the study. Among completers, 22 (75.9 percent; 64.7 percent of the intention-to-treat population) presented >50 percent headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 and the average consumption of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by 9 (31 percent) patients. CONCLUSION: Although limited by the open design, this study provides a pilot data to support the use of quetiapine in preventive treatment of refractory migraine.

INTRODUÇÃO: A migrânea é uma doença neurológica prevalente. Embora a prevenção seja o esteio principal do tratamento, alguns pacientes são refratários aos tratamentos tradicionais. OBJETIVO: Avaliar o uso da quetiapina (QTP) no tratamento preventivo da migrânea refratária definida como ausência de resposta ao uso prévio da combinação de atenolol com nortriptilina e flunarizina. MÉTODO: Trinta e quatro pacientes consecutivos (30 mulheres e 4 homens) com migrânea (CIC-II) e crises de cefaléia em menos de 15 dias/mês sem uso excessivo de sintomáticos foram estudados. O critério de inclusão principal foi a não obtenção na redução da frequência de cefaléia >50 por cento após 10 semanas de uso da combinação de atenolol (60 mg/dia) + nortriptilina (25 mg/dia) + flunarizina (3 mg/dia). Os pacientes iniciaram a QTP como tratamento único na dose de 25 mg à noite e aumentaram-na até 75 mg. Após 10 semanas de uso, a frequência da cefaléia, o consumo de sintomáticos e os efeitos colaterais foram avaliados. RESULTADOS: Vinte e nove pacientes completaram o estudo. Entre os que completaram, 22 (75.9 por cento; 64.7 por cento dos pacientes que foram incluídos) obtiveram redução da frequência >50 por cento. A frequência média de dias com migrânea por mês decresceu de 10,2 para 6,2. O consumo médio de sintomáticos caiu de 2,3 para 1,2 dias/semana. Efeitos colaterais foram relatados por 9 (31 por cento) pacientes. CONCLUSÃO: Apesar de limitado pela metodologia aberta, esse estudo oferece dados iniciais para a possível utilidade da QTP na prevenção da migrânea refratária.

Effects of psychotropic drugs on the thrombin-induced liberation of arachidonate in human platelets

To compare the effects of chlorpromazine [CPZ], prochlorperazine [PCP], trifluoperazine [TFP], clozapine [CLO], haloperidol [HPD], quetiapine [QTP], pimozide [PMZ], and olanzapine [OLP] as well as the tricyclic antidepressants amitriptyline AMI, imipramine IMI, and nortriptyline NTP on thrombin-induced liberation of arachidonic acid AA in platelets. This work was carried out at the Department of Biomedicine, University of Bergen, Norway in 2006-2007. Human platelets pre labelled with [3H] arachidonate were incubated with thrombin in the absence and presence of the drugs, and the amount of free [3H] arachidonate liberated was determined. Myosin light chain [MLC] phosphorylation was determined in [32P] phosphate-labelled platelets after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of the drugs on the molecular area and surface pressure of phospholipid monolayers were determined in the Langmuir apparatus. All drugs reduced arachidonate liberation with the ranking order of increasing potency: OLP. The mechanisms for reduction of arachidonate liberation is thought to interfere with activation of cytosolic phospholipase A2 [cPLA2] by alteration of the PLA2 phospholipid substrate structure in platelet membranes

Influence of ORM1 polymorphism on serum concentration of free nortriptyline / 药学学报

To study the effect of alpha1-acid glycoprotein 1 (ORM1) polymorphism on the concentration of free nortriptyline in serum, genotyping analysis was employed in ORM1 by sequencing. Eighteen unrelated male adults were chosen and given a single dose of 25 mg nortriptyline orally, then the blood samples were taken at 0, 1, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96 and 168 hours after drug administration. Nortriptyline and 10-OH-nortriptyline in serum and ultrafiltrate were detected for the total and free concentration by using HPLC-MS/MS. Pharmacokinetic parameters were compared among different ORM1 genotypes. No significant differences were shown in the pharmacokinetic parameters of total nortriptyline and 10-OH-nortriptyline. The mean AUC(0-infinity) of free nortritpyline in ORM1 * F/ * F1 subjects was significantly higher than that in ORM1 * F1/ * S and ORM1 * S/ * S subjects [(119.1 +/- 74.4) ng x mL(-1) x h vs (51.4 +/- 23.2) ng x mL(-1) x h and (42.4 +/- 11.6) ng x mL(-1) x h]. The percentage of protein binding in subjects with ORM1 * F1/ * F1 genotype at 2, 3, 4, 6, 8 and 12 h after administration was slightly lower than in those with ORM1 * F1/ * S and ORM1 * S/ * S genotypes while the distinct difference was shown at 4 h (P < 0.05). Different ORM1 genotypes might affect the protein binding percentage and the concentration of serum free nortriptyline. The ability binding to the drug was higher in subjects with ORM1 * S/ * S genotype than in those with other two genotypes, so as to cause the lower concentration of free nortriptyline.

Comparing the efficacy of add-on nortryptiline with triiodothyronine in the management of citalopram-resistant depression

To manage a treatment resistant depression, clinicians may add a second medication to the first antidepressant drug. The aim of the current research was to study the outcome of augmentation of citalopram with nortryptiline or triiodothyronine in a randomized clinical trial. We selected 48 adult outpatients with a diagnosis of non-psychotic major depressive disorder who had not responded to 12 weeks citalopram therapy [40 mg per day]. They were randomly allocated to two groups. One group received nortryiptiline [at a dose of up to 150 mg per day] and the other triiodothyronine [T3] [at a dose of up to 50 micro g per day]. The remission of depression was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression [HRSD-17]. After 8 weeks, the nortriptyline group had a higher remission rate [33.33%] than the triiodothyronine group [17.64%]. The nortriptyline group, however, had a higher drop out rate due to experiencing more side effects. Augmentation of citalopram with nortryptiline seems to be effective in the management of treatment resistant depression. However, one should strike a balance between the efficacy and the tolerability of this approach, as there is a higher chance of experiencing side effects by the patients

Depressão maior e supressão hormonal: resposta com a nortriptilina / Major depression and hormone suppression: response with nortriptiline

CONTEXTO: A relevância da descrição deste caso clínico é demonstrar a importância do uso de nortriptilina em um caso de depressão maior pós-tratamento para endometriose. OBJETIVO: Demonstrar as relações entre o tratamento para endometriose e os transtornos psiquiátricos e o resultado terapêutico que obtivemos com o uso da nortriptilina. MÉTODOS: Entrevista psiquiátrica e avaliação clínica psiquiátrica periódica de uma paciente em tratamento no ambulatório do Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro. RESULTADOS: Mulher de 25 anos que, após início de supressão hormonal com goserelina para o tratamento da endometriose, passou a apresentar sintomatologia depressiva e ansiosa proeminente. Sem melhora com o uso de 20 mg/dia de fluoxetina por 8 semanas, foram prescritos 25 mg/dia de nortriptilina com boa resposta clínica em 2 semanas, mantendo a melhora depois de 16 semanas. CONCLUSÃO: Apesar de apenas a sertralina ter sua eficácia demonstrada na melhora dos sintomas depressivos associados à supressão ovariana, neste caso a nortriptilina demonstrou-se eficaz. Observamos a necessidade de estudos crescentes na área a fim de avaliar outras opções terapêuticas.

BACKGROUND: The relevance of this clinical case report is to emphasize the importance of the use of nortryptiline for major depression after endometriosis treatment. OBJECTIVE: To describe by a case report the relationship between treatment for endometriosis and psychiatric disorders. We will also describe the therapeutic response to nortriptyline. METHODS: Psychiatric interview and periodical clinical psychiatric evaluation for the treatment of a patient in the Outpatient Unit of the Institute of Psychiatry of the Federal University of Rio de Janeiro. RESULTS: An outpatient, fifty-five year-old woman with major depression treated in the Psychiatric Institute of Federal University of Rio de Janeiro. She was being treated for endometriosis with goserelin for hormone suppression when she started to complain of depressive and anxiety symptoms. The patient did not improve with 20 mg/day of fluoxetine for 8 weeks. She improved after 2 weeks using 25 mg/day of nortryptiline. The improvement persisted during our 16 weeks follow-up. CONCLUSION: Although only sertraline has its efficacy demonstrated for depressive symptoms associated with ovarian suppression, in this case nortriptyline was efficient too. We observed the necessity of more studies about this topic in order to better evaluate other therapeutic options.

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.

[ comparsion of nortriptiline and vit B12 effects on diabetic neuropathy]

Diabetes is one of the most prevalent disease in the world.Today there are 100 milion diabetics around the world and in Iran it is about 1.5 milion. The prevalence of symptomatic neuropathy is 15% but with NCV it will increase to 50%. Regarding the suffer produced by neuropathy and that there is no effective treatment for that, this is necessary to investigate new treatment options. This is a clinical trial study, done during a 3 months period in vali-e-asr hospital in year 2004. 100 diabetic patients were selected randomly and divided into two equal groups. A complete sensorimotor assessment was performed and a questionnaire consisting history and clinical symptoms including limb pain, murmur and paresthesia and examinations such as pin prink test, position and vibration assessment, was completed. NCV was also done and blood sugar and HbAlc was measured. In case group 2000 micrograms vit B12 was prescribed twice weekly and in control group 10mg nortiptiline every night was prescribed. After 3 months patients were assessed again. Data was analysed using mean and standard deviation and Chi square, K-S, Leven, T and Mann Whitney tests. Based on visual analage scale the difference between pain number before and after treatment was decreased 3.66 [3.66-4.25] in case and 0.48 [0.54-1.13] in control group [P< 0.0001]. Also the difference between paresthesia number before and after treatment was decreased 2.98 [2.51-3.44] in case and 1.06 [064-1.47] in control group [P< 0.001]. The differene between murmur number before and after treatment was decreased 3.48 [2.93-4.02] in case and 3.48 [2.93-4.02] in control group [P< 0.001]. There was no significant difference between NCV, vibration, position and pin prink test results. Changes in clinical symptoms in case group in comparison to those in control group was significant, but change in physical assessment findings [pin prink, Position, vibration and NCV] was not significant