Specific Targeting of Symptom Domains Other Than Positive Symptoms

Until now, efforts to identify an effective antischizophrenia medication have been directed toward development of a broad-spectrum, disease-specific panacea that would target all relevant symptom domains. Despite the broader spectrum of activity of the second-generation antipsychotic agents in comparison to first-generation drugs, they share the quality of being more effective in reducing positive symptoms than negative or cognitive symptoms. Specific pharmacological strategies directed at each of these other symptom domains are currently under investigation. It is, however, likely to be several years before any of the following strategies (assuming they are effective and safe) will become part of mainstream practice. At this stage, these nonpsychotic domain-specific treatments are conceived as add-on or adjunctive treatments to existing antipsychotic agents.

Specific Treatments for Negative Symptoms. Persistent negative symptoms are a major reason for the significant debilitation associated with schizophrenia; current treatments have only limited efficacy. Several pharmacological strategies to specifically treat negative symptoms have been evaluated with limited success thus far. Over the past decade, agents that stimulate the N-methyl-D-aspartate (NMDA) glutamate receptor have shown promise in this regard (Goff and Coyle, 2001). Partial and full agonists at the glycine site have also been used in conjunction with antipsychotics with some success in reducing negative symptoms. Large-scale studies are ongoing.

Specific Treatments for Cognitive Deficits. Perhaps, to an even greater extent than negative symptoms, cognitive dysfunction is correlated with functional impairment in schizophrenia. While novel antipsychotics are generally more effective than conventional agents in ameliorating cognitive symptoms, their efficacy is only modest. While there is some suggestion that different second-generation drugs may differentially improve various aspects of cognitive dysfunction in schizophrenia (and presumably could be matched to the specific cognitive deficits exhibited by a given patient), definitive data in this regard are lacking.

While several neuropharmacological mechanisms have been proposed to explain the cognitive advantages of the newer antipsychotic agents, none is considered definitive at present. In any event, three specific pharmacological targets to ameliorate cognitive impairments in schizophrenia are currently under study. The first target is the

NMDA receptor, with both partial (D-cycloserine) and full (serine and glycine) agonists at the glycine site being studied; modulators of the glutamatergic AMPA receptor are also being assessed for efficacy in treatment of cognitive deficits. Cholinergic augmentation strategies (Tandon and Greden, 1989; Tandon et al., 1999b) and 5-HT1A agonist strategies (Sumiyoshi et al., 2001) are also currently being investigated in this regard.

Other Pharmacological Targets. In addition to glutamatergic, cholinergic, and other serotonergic targets discussed above, several neuropeptidergic treatment strategies are also being pursued in the treatment of schizophrenia. While many types of agents are being studied, cholecystokinin agonists and neurotensin antagonists currently show greatest promise.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

Get My Free Ebook

Post a comment