Psychopharmacology of depression in the next millennium

Over the last half of the 20th century, there have been a series of psychopharmacologic strategies for treatment of depression. As we approach the next century, new therapies in varying stages of American release are being developed. This review will focus on information available for the following proposed antidepressants: 1) reboxetine, a norepinephrine selective reuptake inhibitor; 2) milnacipran, a combined serotonin/norepinephrine reuptake inhibitor; 3) a new enantiomer of fluoxetine, a selective serotonin reuptake inhibitor; 4) duloxetine, another combined serotonin/norepinephrine reuptake inhibitor; 5) sunepitron, a combined 5-HT1A agonist and a2 antagonist; and 6) MK-869, a substance P inhibitor. Finally, other possible developing directions will be reviewed, including corticotropin-releasing factor.     

Pharmacotherapy of paraphilias in the next millennium

Paraphilias are psychiatric disorders of abnormal sexual behavior whose prevalence has markedly increased during the last decade. Treatment modalities currently used fall into three categories: surgical castration, psychotherapy, and pharmacotherapy. The pharmacological interventions consist of antiandrogens that either completely reduce testosterone secretion and/or antagonize the action of testosterone at the level of the receptor, and psychotropic drugs, namely antidepressants. Cyproterone and medroxyprogesterone acetates are the two antiandrogens more commonly used. They are only effective in relatively high doses, but have a substantial number of severe side effects which has considerably limited their use. Psychotropic drugs may be effective solely in men with a definite obsessive-compulsive disorder component. Because of the erratic results and lack of permanent eradication of the paraphilic manifestations their use in paraphilias is highly controversial. Long-acting gonadotropin-releasing hormone (GnRH) agonist analogues are the most potent antiandrogens, and selectively abolish testosterone secretion in a totally reversible fashion. They are administered parenterally once every 1 to 3 months, and have the fewest side effects. Long-acting GnRH analogues, together with psychotherapy, are highly effective in controlling selected paraphilias (pedophilia, exhibitionism, and voyeurism), and are the most promising mode of therapy in the next millennium. There is an urgent need for good methodological research; carefully designed double-blind controlled studies with a large number of subjects in order to validate or not the use of the various pharmacotherapies.     

Cognitive dysfunction in depression: neurocircuitry and new therapeutic strategies

Major depressive disorder (MDD) is a disabling medical condition associated with significant morbidity, mortality and public health costs. However, neurocircuitry abnormalities underlying depression remain incompletely understood and consequently current treatment options are unfortunately limited in efficacy. Recent research has begun to focus specifically on cognitive aspects of depression and potential neurobiological correlates. Two fundamental types of cognitive dysfunction observed in MDD are cognitive biases, which include distorted information processing or attentional allocation toward negative stimuli, and cognitive deficits, which include impairments in attention, short-term memory and executive functioning. In this article, we present a selective review of current research findings in these domains and examine neuroimaging research that is beginning to characterize the neurocircuitry underlying these biases and deficits. We propose that deficient cognitive functioning, attention biases and the sustained negative affect characteristic of MDD can be understood as arising in part from dysfunctional prefrontal-subcortical circuitry and related disturbances in the cognitive control of emotion. Finally, we highlight potential new pharmacological and non-pharmacological therapeutic strategies for MDD based on an evolving mechanistic understanding of the disorder.     

Mental lexicon research in the new millennium

This article presents an overview of current research on the mental lexicon, as it is represented by articles in the spring 2002 Special Issue of Brain and Language. We examine current findings in terms of language, task, and population effects associated with how words are presented and processed in the mind. We discuss how such mental representations may be linked to neurological instantiations and address the issue of ecological validity in the field. These discussions are organized in order to both provide an overview of the issues and to enable the reader to locate specific articles that bear on these issues. Finally, we present an organizational framework for the characterization of mental lexicon research within which challenges for advancement are isolated.     

Meditating selflessly at the dawn of a new millennium

Increasingly open to question are the efficacies and timing of some traditional, conventional and current meditative techniques. Recent brain research emphasizes that it is important to distinguish between the Self-centred (egocentric) and other-centred (allocentric) streams of processing. It also proves useful to view as complementary the assets of the concentrative and receptive styles of meditation, especially when one's practices cultivate an appropriate balance between their top-down and bottom-up systems of attentive processing. From this neural perspective, Part I ventures a small sample of empirical suggestions. Some of these could help practitioners engage in more open, effortless, choiceless, varieties of receptive meditation–indoors and outdoors. Part II discusses recent research that illuminates issues arising at the interface between Self and other. The evidence suggests how a balanced attentiveness might enable long-term meditators to enhance mindfulness of the present moment, while simultaneously becoming much less fearful and, ultimately, freer to openly express their most objective, innate instincts of selfless compassion.

The art of Progress is to preserve order amid change and to preserve change amid order. (Alfred North Whitehead 1861–1947)