摘要:

Bipolar (manic-depressive) disorder is one of the most common of the severe mental illnesses. Officially recognised forms comprise type I (with mania), type II (with hypomania), cyclothymia and a rapid-cycling subtype. International lifetime prevalence estimates are 1 to 5% of the general population, and bipolar disorder accounts disproportionately for idiopathic psychoses. Psychiatric and substance-abuse comorbidities are common complications, and mortality rates are increased as a result of high suicidal risks, accidents, complications of substance abuse and increased fatality of stress-sensitive medical illnesses. Complex and labile symptomatic presentations, a tendency for patients to deny illness and reject treatment, and diagnostic heterogeneity severely complicate the design, conduct and interpretation of experimental treatment trials in bipolar disorder.Progress in the short-term treatment of mania with certain antiepileptic drugs and atypical antipsychotic agents has advanced greatly in recent years; however, long-term treatment trials other than with lithium remain rare, as are studies of type II disorder, bipolar depression and mixed states, and there is limited information on treatment effectiveness against comorbidity, dysfunction and mortality. There is a growing realisation that bipolar disorder represents a major, largely unmet, international public health challenge and that innovative methods for carrying out reliable and generalisable long-term pharmacological treatment trials, alone and in combination with cost-effective psychosocial and rehabilitative interventions, are urgently required.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Anxiety disorders are among the most common psychiatric disorders that affect all age groups of the general population. Currently, the preferred treatment is with pharmacological drugs that have antidepressant or anti-anxiety properties. However, these agents have numerous and often serious adverse effects, including sedation, impaired cognition, ataxia, aggression, sexual dysfunction, tolerance and dependence. Withdrawal reactions on termination after long-term administration are also a major limiting factor in the use of these agents.Herbal remedies, including kava (Piper methysticum), have been shown to be effective as alternative treatments, at least in mild to moderate cases of anxiety. Kava is a social and ceremonial herb from the South Pacific. It is available in the west as an over-the-counter preparation. Its biological effects, due to a mixture of compounds called kavalactones, are reported to include sedative, anxiolytic, antistress, analgesic, local anaesthetic, anticonvulsant and neuroprotective properties.The pharmacological properties of kava are postulated to include blockade of voltage-gated sodium ion channels, enhanced ligand binding to γ-aminobutyric acid (GABA) type A receptors, diminished excitatory neurotransmitter release due to calcium ion channel blockade, reduced neuronal reuptake of noradrenaline (norepinephrine), reversible inhibition of monoamine oxidase B and suppression of the synthesis of the eicosanoid thromboxane A2, which antagonises GABAAreceptor function.Clinical studies have shown that kava and kavalactones are effective in the treatment of anxiety at subclinical and clinical levels, anxiety associated with menopause and anxiety due to various medical conditions.Until recently, the adverse effects attributed to kava use were considered mild or negligible, except for the occurrence of a skin lesion. This disorder, called kava dermopathy, occurs only with prolonged use of large amounts of kava and is reversible on reduced intake or cessation. Rare cases of interactions have occurred with pharmaceutical drugs that share one or more mechanisms of action with the kavalactones. In the past few years, about 35 cases of severe liver toxicity associated with kava intake have been reported in Europe and the US. However, a direct causal relationship with kava use has been difficult to establish in the majority of the cases, and there is insufficient evidence to implicate kava as the responsible agent. Nevertheless, until further research clarifies any causality, kava should be used with caution.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Female hypoactive sexual desire disorder (HSDD) may occur in up to one-third of adult women in the US. The essential feature of female HSDD is a deficiency or absence of sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty.The evaluation of female HSDD generally requires careful and thoughtful consideration of the patient and the multitude of factors that impact on the various components of adult female sexual desire. Several female reproductive life experiences may uniquely affect sexual desire. These events include menstrual cycles, hormonal contraceptives, postpartum states and lactation, oophorectomy and hysterectomy, and perimenopausal and postmenopausal states. Sexual dysfunctions in women have strong positive associations with low feelings of physical and emotional satisfaction and low feelings of happiness. Thus, female HSDD can greatly impact on quality of life.In this article, treatment options are discussed with special attention to significant reproductive life events that may impact on sexual desire in adult women. Depending on the particular phase of reproductive life that a woman is experiencing, different recommendations are made. Various options in the treatment of HSDD in women include lifestyle changes, treatment of coexisting medical or psychiatric disorders, switching or discontinuing medications that could impact on sexual desire, hormone therapy and marital therapy. Clinical trials are presently underway to assess medications that may potentially benefit female patients with HSDD.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

The treatment of women of childbearing age who have epilepsy raises many questions because of the interactions between epilepsy, antiepileptic therapy and different aspects of reproductive life. Menstrual cycle disorders and reduced fertility have been partially ascribed to antiepileptic drugs (AEDs). Furthermore, most AEDs induce the cytochrome P450 (CYP) enzymatic system, altering the metabolism of sex hormones and contributing to the failure of oral contraceptives.Pregnancy represents, in this context, the most critical period because of the well known teratogenic potential of all established AEDs. For most of these drugs no specific patterns of malformations have been identified, although during the past few decades basic knowledge has been acquired, particularly concerning the mechanisms of AED-induced teratogenesis and related risk factors. These issues form the basis of the current guidelines for the management of epilepsy in pregnant women.In the past decade, several new AEDs have been introduced into clinical practice. For a number of reasons, these drugs appear to be more favourable than the older ones as treatments for epilepsy in women of childbearing age. They possess a good pharmacokinetic profile that makes them more stable during pregnancy, and they have a low potential for interaction with other drugs. They are also less likely than the older AEDs to be metabolised to compounds that are teratogenic. Furthermore, most of them do not possess antifolate properties. With the exception of topiramate and vigabatrin, the newer AEDs do not appear to be teratogenic in animals when administered in subtoxic doses. However, animal teratology may not be a reliable predictor of human teratogenicity, and there is a significant lack of information regarding the teratogenic profile of these newer agents in humans. Because clinical experience with these agents is limited, it is advisable to avoid exposure of the embryo to these drugs when pregnancy is planned.The establishment of pregnancy registries could allow for the rapid collection of data related to the administration of new AEDs in pregnancy and the outcomes of such exposure.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Psychiatric disorders themselves and treatment with conventional antipsychotic medications have in a number of early studies been associated with venous thromboembolism. In general, information on the relationship between antipsychotics and this possible adverse effect is in the form of case reports and open cross-sectional studies. However, recently the association between conventional antipsychotics and venous thrombosis has been strengthened as a result of the publication of a large, nested, case-control study. In this study, low-potency antipsychotic drugs were more strongly associated with venous thrombosis than high-potency drugs. In addition, recent epidemiological data support an association between the atypical antipsychotic agent clozapine and venous thromboembolism. The risk for venous thromboembolism seems to be highest during the initial months of treatment with antipsychotics.The biological mechanisms responsible for this possible adverse drug reaction are unknown, but a number of hypotheses have been suggested. The increased risk may be the result of drug-induced sedation, obesity, hyperleptinaemia, antiphospholipid antibodies and increased activity in the coagulation system. The association could also be related to underlying risk factors present in patients with psychosis such as smoking.Despite the limitations of present knowledge, clinicians should be aware of this possible adverse drug reaction and should consider interrupting or changing the antipsychotic regimen in patients in whom this reaction is suspected. More studies are needed in order to further elucidate this adverse effect, particularly to determine the incidence rate, possible predisposing factors and the biological mechanisms involved.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

▴ Aripiprazole is a quinolinone derivative and the first of a new class of atypical antipsychotics. The drug has partial agonist activity at dopamine D2and serotonin 5-HT1Areceptors, and is also an antagonist at 5-HT2Areceptors.▴ In patients with acute relapse of schizophrenia or schizoaffective disorder, aripiprazole 15 to 30 mg/day was at least as effective as haloperidol 10 mg/day and had similar efficacy to risperidone 6 mg/day in well designed, 4-week, placebo-controlled trials.▴ Negative symptoms improved earlier in the aripiprazole than the risperidone group. Efficacy of aripiprazole was observed at week 1 in several trials and was sustained throughout the study periods.▴ Aripiprazole was superior to placebo in a 26-week trial in patients with stable, chronic schizophrenia. In a 52-week trial involving patients with acute relapsing disease, aripiprazole was similar to haloperidol as assessed by time to failure to maintain response and was superior in ameliorating negative and depressive symptoms.▴ The incidence of extrapyramidal symptoms during aripiprazole therapy was similar to that with risperidone and placebo but lower than with haloperidol.▴ Compared with placebo, the proportion of patients with increased plasma prolactin levels and QTc prolongation was similar in patients treated with aripiprazole 15 to 30 mg/day but was significantly increased with haloperidol and risperidone.Table.Features and properties of aripiprazole (OPC 14597)Figure. Aripiprazole

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Sertraline is a selective serotonin reuptake inhibitor (SSRI) with well established antidepressant and anxiolytic activity. Results from several well designed trials show that sertraline (50−200 mg/day) is effective in the treatment of major depressive disorder in elderly patients (≥60 years of age). Primary endpoints in most studies included the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression score and the Montgomery-Åsberg Depression Rating Scale. Sertraline was significantly more effective than placebo and was as effective as fluoxetine, nortriptyline and imipramine in elderly patients. During one trial, amitriptyline was significantly more effective than sertraline (mean reduction from baseline on one of six primary outcomes [HDRS]), although no quantitative data were provided. Subgroup analysis of data from a randomised, double-blind trial in elderly patients with major depressive disorder suggests that vascular morbidity, diabetes mellitus or arthritis does not affect the antidepressant effect of sertraline.Secondary endpoints from these clinical trials suggest that sertraline has significant benefits over nortriptyline in terms of quality of life. In addition, significant differences favouring sertraline in comparison with nortriptyline and fluoxetine have been recorded for a number of cognitive functioning parameters.Sertraline is generally well tolerated in elderly patients with major depressive disorder and lacks the marked anticholinergic effects that characterise the adverse event profiles of tricyclic antidepressants (TCAs). The most frequently reported adverse events in patients aged ≥60 years with major depressive disorder receiving sertraline 50−150 mg/day were dry mouth, headache, diarrhoea, nausea, insomnia, somnolence, constipation, dizziness, sweating and taste abnormalities. The tolerability profile of sertraline is generally similar in younger and elderly patients.Sertraline has a low potential for drug interactions at the level of the cytochrome P450 enzyme system. In addition, no dosage adjustments are warranted for elderly patients solely based on age.ConclusionSertraline is an effective and well tolerated antidepressant for the treatment of major depressive disorder in patients aged ≥60 years. Since elderly patients are particularly prone to the anticholinergic effects of TCAs as a class, SSRIs such as sertraline are likely to be a better choice for the treatment of major depressive disorder in this age group. In addition, sertraline may have advantages over the SSRIs paroxetine, fluoxetine and fluvoxamine in elderly patients because of the drug's comparatively low potential for drug interactions, which is of importance in patient groups such as the elderly who are likely to receive more than one drug regimen.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS