Citicoline: pharmacological and clinical review, 2022 update. / Citicolina: revisión farmacológica y clínica, actualización 2022.

This review is based on the previous one published in 2016 (Secades JJ. Citicoline: pharmacological and clinical review, 2016 update. Rev Neurol 2016; 63 (Supl 3): S1-S73), incorporating 176 new references, having all the information available in the same document to facilitate the access to the information in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications.

TITLE: Citicolina: revisión farmacológica y clínica, actualización 2022.Esta revisión se basa en la publicada en 2016 ­Secades JJ. Citicolina: revisión farmacológica y clínica, actualización 2016. Rev Neurol 2016; 63 (Supl 3): S1-S73­, e incorpora 176 nuevas referencias aparecidas desde entonces, con toda la información disponible para facilitar el acceso a toda la información en un único documento. La revisión se centra en las principales indicaciones del fármaco, como los accidentes cerebrovasculares agudos y sus secuelas, incluyendo el deterioro cognitivo, y los traumatismos craneoencefálicos y sus secuelas. Se recogen los principales aspectos experimentales y clínicos en estas indicaciones.

Citicolina: revisión farmacológica y clínica, actualización 2022 / Citicoline: pharmacological and clinical review, 2022 update

Esta revisión se basa en la publicada en 2016 –Secades JJ. Citicolina: revisión farmacológica y clínica, actualización 2016. Rev Neurol 2016; 63 (Supl 3): S1-S73–, e incorpora 176 nuevas referencias aparecidas desde entonces, con toda la información disponible para facilitar el acceso a toda la información en un único documento. La revisión se centra en las principales indicaciones del fármaco, como los accidentes cerebrovasculares agudos y sus secuelas, incluyendo el deterioro cognitivo, y los traumatismos craneoencefálicos y sus secuelas. Se recogen los principales aspectos experimentales y clínicos en estas indicaciones

This review is based on the previous one published in 2016 (Secades JJ. Citicoline: pharmacological and clinical review, 2016 update. Rev Neurol 2016; 63 (Supl 3): S1-S73), incorporating 176 new references, having all the information available in the same document to facilitate the access to the information in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications.(AU)

Valproate-induced delirium in a demented patient.

In this study we report a case of valproate-induced delirium in a patient affected with Alzheimer's disease (AD). A 75-year-old woman with AD presented moderate cognitive impairment associated to behavioral disorders, characterized by aggression, agitation, severe insomnia. She was treated with galantamine, promazine, acetylsalicylic acid and pantoprazole. Since behavioral disorders worsened more and more, home neurological consultation was asked. The neurologist prescribed a mood stabilizer, sodium valproate 500 mg daily for the first week and then, twice a day and stopped promazine. After an apparent initial benefit, about 16 days later, patient suddenly developed hyperactive delirium. It was characterized by worsening of insomnia and agitation, severe confusion, delusions, visual hallucinations alternated to sedation. She became progressively unable to walk and completely dependent in daily living activities. An urgent geriatric consultation was performed at patient's home; physical examination showed mild dehydration, normal blood pressure. Oxygen saturation and electrocardiogram were normal. Sodium valproate was immediately stopped and rehydration was performed. The patient was admitted to a Geriatric Unit, where organic and metabolic damages were excluded. During the hospital stay the patient was agitated, aggressive, confused; intramuscular haloperidol 5mg and saline intravenous infusion 1500 cc daily were performed, they were partly successful. Three days after she was discharged and continued treatment with oral haloperidol 5mg daily. One week later the patient recovered and she is at present healthy. This is a case report of valproate-induced delirium. The Naranjo scale scored 7, classifying this drug-related event as probable. The present case report suggests the need for minimizing the use of psychoactive drugs in elderly demented patients, whether possible; age-related changes in pharmacokinetics and pharmacodynamics suggest the opportunity of a careful evaluation and a slow titration of treatments in these patients.

Management of heart failure in elderly people.

AIMS: To review currently available knowledge on presentation, clinical features and management of heart failure (HF) in elderly people. METHODS: To review currently available evidence, we performed a thorough search of several evidence-based sources of information, including Cochrane Database of Systematic Reviews, Clinical Evidence, Evidence-based guidelines from National Guidelines Clearinghouse and a comprehensive MEDLINE search with the MeSH terms: 'heart failure', 'elderly' and 'management'. RESULTS: A number of features of ageing may predispose elderly people to HF, and may impair the ability to respond to injuries. Another hallmark of elderly patients is the increasing prevalence of multiple coexisting chronic conditions and geriatric syndromes that may complicate the clinical presentation and evolution of HF. Although diagnosis may be challenging, because atypical symptoms and presentations are common, and comorbid conditions may mimic or complicate the clinical picture, diagnostic criteria do not change in elderly people. Drug treatment is not significantly different from that recommended in younger patients, and largely remains empiric, because clinical trials have generally excluded elderly people and patients with comorbid conditions. Disease management programmes may have the potential to reduce morbidity and mortality for patients with HF. CONCLUSIONS: Heart failure is the commonest reason for hospitalisation and readmission among older adults. HF shows peculiar features in elderly people, and is usually complicated by comorbidities, presenting a significant financial burden worldwide, nevertheless elderly people have been generally excluded from clinical trials, and thus management largely remains empiric and based on evidence from younger age groups.

Effectiveness and safety of hypnotic drugs in the treatment of insomnia in over 70-year old people.

Good sleep is an important index of the quality of life in people and above all in old subjects. Among all the symptoms reported to general practitioner, insomnia is at the 3(rd) place and this is present in particular in the elderly. In elderly people high comorbidity and polytreatment are often present. We have studied 60 elderly people with history of insomnia and concomitant diseases: depression, dementia and behavioral disturbances. All the patients of the present study were visited in our outpatients' department. Three hypnotic drugs were used for the treatment of insomnia: zolpidem, or triazolam, or oxazepam, respectively at doses of 10mg/day, 0.125-0.25mg/day and 15.0mg/day. All the three drugs showed to be effective and safe; no paradoxical effects were observed.

Anticholinergic drug-induced delirium in an elderly Alzheimer's dementia patient.

Drug-induced delirium is a common matter in the elderly and anticholinergics, together with a number of different drugs, may significantly contribute to the delirium onset, especially in demented people. We report a case of a probable anticholinergic drug-induced delirium in an elderly patient. An 80-year-old man with Alzheimer's dementia presented with wandering, depressed mood with crying, somatic worries, anedonism and suicide recurrent ideas. A first external psychiatric assessment led to the diagnosis of melancholic depression and therapy with haloperidol 2mg/day, orphenadrine 100mg daily, amitriptyline 40 mg/day, lorazepam 2mg/day was started. Two weeks later patient suddenly developed delirium, characterized by nocturnal agitation, severe insomnia, daytime sedation, confusion, hallucinations and persecutory delusions. These symptoms progressively worsened, with the consequent caregiver's stress. A geriatric consultation excluded the main causes of delirium, therefore both Operative Units of Pharmacovigilance and Psychiatry were activated, for a clinical pharmacological and psychiatric assessment. Haloperidol, amitriptyline and orphenadrine were promptly dismissed. The patient began a treatment with quetiapine 25mg/day for two days, then twice a day, and infusion of saline 1000 ml/day for two days; psychiatric symptoms gradually diminished and therapy with galantamine was begun. We postulate that this clinical report is suggestive for an anticholinergic drug- induced delirium since the Naranjo probability scale indicated a probable relationship between delirium and drug therapy. In conclusion, a complete geriatric, pharmacological, and psychiatric evaluation might be necessary in order to reduce the adverse drug reactions in older patients treated with many drugs.

[Evaluation of thyroid function in a group of over-eighty year-old people]. / Valutazione della funzionalità tiroidea in un gruppo di ultraottantenni.

AIM: A number of studies has shown that during aging thyroid presents some structural changes, whilst no data agree about secretory activity. The aim of the present study was to evaluate thyroid function in a group of healthy over-80 years old people vs a group of young subjects. METHODS: This study was performed on 48 old people, 33 women (68.75%) and 15 men (31.25%), mean age 86.38+/-5.20 years old and 43 young subjects, mean age 33.35+/-3.75 years old; all of them were euthyroid and were not affected with any acute or chronic diseases and did not take any drugs which could interfere with thyroid function. A blood sample was taken from each patient, for dosing TT3, TT4, FT3, FT4, TSH, TgAb, TPOAb. RESULTS: The results of the present study show low serum levels of TT3 in healthy over-80 year old people compared to young people, even if serum levels of TT4, FT3, FT4, TSH have no significant changes. CONCLUSIONS: Functional reduction in thyroid activity during aging has not to be considered responsible for senile involution; it is more appropriate to define it as the expression of a metabolic slow down in the elderly.

Use of zolpidem in over 75-year-old patients with sleep disorders and comorbidities.

The aim of the present study was to evaluate the efficacy and safety of zolpidem in elderly subjects with disorders of sleep and comorbidities. The patients of this study had to present the following requirements: age over 70 years, reported disorders of sleep such as insomnia, and they had to be affected with diabetes and arterial hypertension. Patients presenting diseases that could interfere with sleep, i.e., anxiety, depression, panic attacks,alcohol abuse, some drugs were excluded from the study. All the jobs potentially causing insomnia carried out in the past from the patients were considered, too. A questionnaire of sleep was administered to all the patients (World Psychiatric Association: WPA, 1971).Insomnia, whenever present, was classified according to the criteria of the American Sleep Disorders (ASD) Society and the American Professional Sleep Society (APSS). The following scales were also administered: instrumental activities of daily living scale (IADL),activities of daily living (ADL), geriatric depression scale (GDS), cumulative illness rating scale (CIRS), short portable mental status questionnaire (SPMSQ), mini nutritional assessment (MNA), disease medical index (DMI), sleep questionnaire, social and environmental status. Two groups of patients were evaluated. Group A: 50 patients, 35 women and 15 men, mean age 78.9 years, with a history of insomnia, and Group B 30 patients, 20 women and 10 men, mean age 78.4 years, with onset of insomnia in the last three weeks. The two groups were further divided into three subgroups, diabetic, hypertensive and healthy patients. Zolpidem showed to be effective and well tolerated in both groups of patients.

Comparison of the efficacy of new and conventional antipsychotic drugs in the treatment of behavioral and psychological symptoms of dementia (BPSD).

This double-blind study evaluated the efficacy and safety of risperidone or olanzapine vs. promazine in the treatment of behavioral and psychological symptoms in dementia(BPSD). Patients were required to be 65 years or older, to have DSM-IV diagnoses of Alzheimer's disease (AD), vascular dementia (VD) or a combination of both. A brain computerized tomography (CT) was performed for all the patients; 60 demented patients,27 men (45 %) and 33 women (55 %) were selected for this study. The University of California Los Angeles neuropsychiatric inventory (NPI) was administered at baseline, then after 4 and 8 weeks. Patients had at least a score of 24 or more. The Hoehn and Yahr scale was used for evaluating parkinsonism. The scales were administered by an examinator who was not aware of the kind of treatment of the patients. After a wash-out period of 10 days,20 patients, 9 men and 11 women, mean age 76.6 +/- 6.0 years, were randomly assigned torisperidone 1 mg daily in divided doses (morning and bedtime) (Group A); 20 patients, 9 men and 11 women, mean age 82.5 +/- 9.3 years were randomly assigned to olanzapine 5mg at bedtime (Group B), and 20 patients, 9 men and 11 women, mean age 77.6 +/- 4.6 years, were randomly assigned to promazine 50 mg daily (morning and bedtime) (Group C). In case of lack of clinical response, after 4 weeks, the dose could be increased to 2 mg/day of risperidone, 10 mg/day of olanzapine, and to 100 mg/day of promazine in the respective groups. Repeated measures ANOVA was used for the statistical analysis of rating scales over time (baseline, 4 and 8 weeks). At the end of the 8th week, a global improvement was obtained in 80% of patients treated with risperidone and olanzapine, vs. 65 % of patients treated with promazine (p < 0.01). The results show that risperidone in doses of 1-2 mg/day and olanzapine in doses of 5-10 mg/day are effective and safe in the treatment of BPSD. Risperidone presents a major and dose-dependent antidopaminergic action and seems to be preferable when hallucinations and delusions are prevailing symptoms, even if it gives good results on aggression and wandering. Olanzapine seems to be faster in its sedative effect, probably for H1 receptor blockade. Moreover, 5-HT6 antagonism may favor acetylcholine release and this explains why these patients have not presented a cognitive worsening. However, both drugs are comparable or even superior to promazine, with significantly fewer side effects of both anticholinergic and extrapyramidal character.

[Falls in the elderly]. / Le cadute nell'anziano.

Falls are the main causes of accidental death and disability in elderly people, since they may especially cause hip fractures and a number of related complications. Available incidence estimates are surely in defect, because falls are often omitted both by patients, their family and caregivers. Risk factors may be classified in intrinsic and extrinsic; the former include muscular and osteoarticular diseases or other favouring conditions, whilst the latter include environmental or iatrogenic factors, such as drugs or alcohol consumption. Extrinsic factors may be rapidly modified in the elderly and thus prevented. In fact, prevention of falls is the main intervention of geriatrist, both at patient's home and if patient is hospitalized. In order to reduce the risk of falls, it is sometimes sufficient to stop a treatment or to reduce the doses of drugs causing sedation or orthostatic hypotension, to avoid if possible, the use of sedative-hypnotics, to use non-pharmacological methods for treating insomnia. The introduction of the necessary changes in the environment, the promotion of physical activity, the individuation of the subjects with a high risk of falls and the use of hip protectors are useful means for preventing falls and avoiding their harmful consequences.

[Isolated systolic hypertension in the elderly]. / L'ipertensione sistolica isolata dell'anziano.

Isolated systolic hypertension is the most common type of hypertension in the elderly. A number of trials have widely shown that it is an independent risk factor for cardiovascular morbidity and mortality. This review focuses the prevalence of isolated systolic hypertension, its pathophysiology, diagnosis and treatment. The optimal treatment strategy is to maximize reduction in systolic blood pressure and to minimize reduction in diastolic blood pressure. All classes of antihypertensive agents can be used, but calcium antagonists, ACE-inhibitors and, more recently, the angiotensin II antagonists appear to be more successful in improving large artery stiffness and therefore are especially useful in treating isolated systolic hypertension in the elderly. A careful evaluation and treatment has to be made in particular in those patients with more risk factors, in order to choose the most appropriate drug and to avoid dangerous drug-drug interactions where polypharmacy occurs.

[The longevity of centenarians]. / Longevità familiare degli ultracentenari.

BACKGROUND: The increase of mean lifetime has also given rise to an increase in the number of centenarians; such a circumstance finds its explanation in an improvement in hygienic conditions in addition to the progress in the medical field. The aim of this retrospective study is the attempt to identify the probable factors encouraging the achievement of an extreme longevity. METHODS: The study was carried out, on a house to house basis, on a sample of 46 calabrian centenarians. In order to demonstrate the hereditary component, the frequency of the centenarians among the closest relatives was considered, through birth and death certificates. The case history questionnaire used most geriatric and gerontological centres associated to the national project Italian Multicentric Study on Centena-rians was used. RESULTS: The profile of our long-lived subject has allowed us to underline the importance of the environmental factor as well as the hereditary component. In most cases these subjects live with their family and have excellent relationships, receiving a great deal of attention from the persons with which they live. CONCLUSIONS: The authors have therefore reached the conclusion by stressing the importance of both factors (hereditary and genetic); however a type of intervention in order to lengthen the mean lifetime is hypothesized exclusively in the environment field through the elimination of certain risk factors.

7-Nitroindazole potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice.

7-Nitroindazole, a selective neuronal nitric oxide synthase inhibitor (25-200 mg kg(-1), intraperitoneally (i.p.)) antagonized audiogenic seizures in DBA/2 mice in a dose-dependent manner. We investigated the effects of 7-nitroindazole at a dose of 25 mg kg(-1) i.p., which per se did not show anticonvulsant activity against audiogenic seizures in DBA/2 mice, on the antiseizure activity of some conventional antiepileptic drugs. 7-Nitroindazole sometimes potentiated the anticonvulsant activity of carbamazepine, diazepam, lamotrigine, phenytoin, phenobarbital and valproate against audiogenic seizures in DBA/2 mice. The degree of potentiation by 7-nitroindazole was greatest for phenobarbital and diazepam, less for valproate and least for carbamazepine, lamotrigine and phenytoin. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment with diazepam+7-nitroindazole, phenobarbital+7-nitroindazole or valproate+7-nitroindazole was more favourable than that of the diazepam+vehicle, phenobarbital+vehicle or valproate+vehicle treatment. The results indicate that 7-nitroindazole is able to increase the protective activity of some conventional antiepileptics and this effect appears not to result only from the impaired synthesis of nitric oxide. In fact, mice receiving 7-nitroindazole (25 mg kg(-1), i.p.) and L-arginine (30 microg/mouse, intracerebroventricularly (i.c.v.) did not show significant changes of ED(50) values in comparison to those of related groups of animals treated with 7-nitroindazole and anticonvulsants. 7-Nitroindazole was able to increase the brain levels of dopamine and noradrenaline and its anticonvulsant effects and changes in catecholamine content were antagonized by pretreatment with alpha-methyl-paratyrosine, an agent inhibiting the synthesis of catecholamines. The fact that alpha-methyl-paratyrosine reverses concomitantly both the increase in brain levels of dopamine and noradrenaline and the anticonvulsant properties of 7-nitroindazole strongly suggests an important role of catecholamines in the antiseizure activity of 7-nitroindazole. Since 7-nitroindazole did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. 7-Nitroindazole did not significantly affect the hypothermic effects of the anticonvulsant compounds studied. 7-Nitroindazole showed an additive effect when administered in combination with some classical anticonvulsants, most notably diazepam, phenobarbital and valproate and its activity could be, in part, due to an increase of monoamine levels.

Conventional and new antidepressant drugs in the elderly.

Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and nonsuicide mortality. Therefore, it is very important to make an early diagnosis and a suitable pharmacological treatment, not only for resolving the acute episode, but also for preventing relapse and enhancing the quality of life. Age-related changes in pharmacokinetics and in pharmacodynamics have to be kept into account before prescribing an antidepressant therapy in an old patient. In this paper some of the most important and tolerated drugs in the elderly are reviewed. Tricyclic antidepressants have to be used carefully for their important side effects. Nortriptyline, amytriptiline, clomipramine and desipramine as well, seem to be the best tolerated tricyclics in old people. Second generation antidepressants are preferred for the elderly and those patients with heart disease as they have milder side effects and are less toxic in overdose and include the so called atypicals, such as selective serotonin reuptake inhibitors, serotonin noradrenalene reuptake inhibitors and noradrenaline reuptake inhibitors. Monoamine oxidase (MAO) inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy; the last generation drugs (reversible MAO inhibitors), such as meclobemide, seem to be very successful. Mood stabilizing drugs are widely used for preventing recurrences of depression and for preventing and treating bipolar illness. They include lithium, which is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients for its side effects, the anticonvulsants carbamazepine and valproic acid. Putative last generation mood stabilizing drugs include the dihydropyridine L-type calcium channel blockers and the anticonvulsants phenytoin, lamotrigine, gabapentin and topiramate, which have unique mechanisms of action and also merit further systematic study. Psychotherapy is often used as an adjunct to pharmacotherapy, while electroconvulsant therapy is used only in the elderly patients with severe depression, high risk of suicide or drug resistant forms.

Treatment of epilepsy in the elderly.

Management of epilepsy in the elderly involves many challenges, including the presence of concomitant diseases, polypharmacy and changes in body physiology. Age-related changes in pharmacokinetics and pharmacodynamics have to be taken into account in order to avoid potentially severe adverse drug reactions in elderly people. The present study reviews the most commonly used antiepileptic drugs (AEDs) in the elderly. Because some AEDs may induce the metabolism of other agents and reduce the effectiveness of several drugs, the physicians have to carefully evaluate concomitant drugs being administered. Moreover, the main problems appear to be when beginning therapy, the first choice drug, the appropriate dosage and pharmacologic compliance. Elderly patients must be screened for hepatic and renal functions before beginning a treatment with an AED, carefully interviewed to reduce complaints for drug side-effects which may negatively influence compliance and monitored for total and free blood levels. Besides the 'classic' AEDs, such as phenytoin, phenobarbital, carbamazepine, valproic acid, primidone and benzodiazepines, the review shows the possible advantages of new AEDs, such as felbamate, gabapentin, lamotrigine, oxcarbazepine and gamma-vinyl-GABA, which may be used in the elderly too for their good tolerability. A careful control of drug assumption is requested in the elderly, especially when it is difficult to achieve seizure control.

Effects of some AMPA receptor antagonists on the development of tolerance in epilepsy-prone rats and in pentylenetetrazole kindled rats.

The non-selective alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor antagonists, 2,3-benzodiazepine derivatives CFM-1 (3,5-dihydro-7,8-dimethoxy-1-phenyl-4H-2,3-benzodiazepin-4-one) and CFM-2 (1-(4'-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin -4-one), following intraperitoneal (i.p.) administration, were studied against audiogenic seizures in genetically epilepsy-prone rats (GEPRs) or pentylenetetrazole induced kindling in rats. After acute i.p. administration the ED50 values of CFM-1 against the clonic and tonic phases of the audiogenic seizures 30 min after pretreatment were 40 (16-100) and 13 (8-25) micromol kg(-1), respectively. The animals used for chronic study were treated i.p. daily (at 10 h) for 4 weeks with CFM-1 (20 or 50 micromol kg(-1)). Chronic treatment for 2 weeks with CFM-1 gave ED50 values against clonic and tonic seizures of 39 (22-69) and 16 (8-25) micromol kg(-1), respectively, whereas chronic treatment for 4 weeks gave ED50 values against clonic and tonic seizures of 42 (18-98) and 17 (7-41.3) micromol kg(-1), respectively. The duration of anticonvulsant activity observed between 0.5 and 4 h following administration of CFM-1 was similar for acute and chronic treatment. Two groups of Sprague-Dawley rats received CMF (20 or 50 micromol kg(-1)) 30 min before a subconvulsant dose of pentylentetrazole (25 mg kg(-1) i.p.) which is able to increase seizure severity in control animals (i.e., chemical kindling). Pretreatment with CFM-2 delayed the progression of seizure rank during repeated administration of pentylentetrazole. At the end of the period of repeated pentylentetrazole treatment (6 weeks) the mean seizure score was 0 in vehicle treated controls, 4.3 in animals treated with vehicle + pentylentetrazole, 2.2 in rats treated chronically with CFM-2 (20 micromol kg(-1) i.p.) + pentylentetrazole and 1.0 in rats treated repeatedly with CFM-2 (50 micromol kg(-1) i.p.) + pentylenetetrazole. CFM-2 was also able to antagonize the long-term increase in sensitivity of the convulsant effects of GABA function inhibitors in pentylentetrazole-kindled animals. Thus, the administration of a challenge dose of pentylentetrazole (15 mg kg(-1) i.p.) or picrotoxin (1.5 mg kg(-1) i.p.) 15 or 30 days after the end of the repeated treatment showed that animals treated with CFM-2 were significantly protected against seizures induced by pentylentetrazole or picrotoxin. The data suggest that, following repeated treatment, tolerance to the novel AMPA receptor antagonists does not develop (CFM-1 in genetically epilepsy-prone rats and CFM-2 in the pentylentetrazole kindling model of epilepsy). Thirteen minutes after drug injection on days 1, 14 and 28 of chronic treatment the motor impairment induced by these compounds was studied with a rotarod apparatus. The TD50 values for CFM-1 or CFM-2-induced impairment of locomotor performance were similar following acute and repeated treatment. The data also suggest that some novel 2,3-benzodiazepines may have clinical potential for some types of epilepsy.

Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice.

Gabapentin (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in Dilute Brown Agouti DBA2J (DBA/2) mice in a dose-dependent manner. Gabapentin at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The potentiation induced by gabapentin was greatest for diazepam, phenobarbital and valproate, less for felbamate and phenytoin and least for carbamazepine and lamotrigine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of the above drugs + gabapentin was more favourable than that of the same drugs + saline. Since gabapentin did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. However, the possibility that gabapentin can modify the clearance from the brain of the anticonvulsant drugs studied can not be excluded. In addition, gabapentin did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, gabapentin showed an additive effect when administered in combination with certain classical anticonvulsants, most notably diazepam, phenobarbital, felbamate, phenytoin and valproate.

Antidepressant drugs in the elderly.

1. In this article some of the most important and tolerated drugs in the elderly are reviewed. 2. Tricyclic antidepressants have to be used carefully because of their important side effects. Nortriptyline and desipramine appear to be the best tolerated tricyclics in old people. 3. Second generation antidepressants are preferred for the elderly and those patients with heart disease as they have milder side effects and are less toxic in overdose. 4. MAO inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy and the last generation drugs (reversible MAO inhibitors), such as moclobemide, seem to be very successful. 5. Lithium is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients due to its side effects. 6. Psychotherapy is often used as an adjunct to pharmacotherapy, while electroconvulsant therapy is used only in the elderly patients with severe depression, high risk of suicide, or drug-resistant forms.