Cognitive dysfunction treatment

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

A basic ethical issue in several areas of psychiatric research is whether participants are able to provide informed consent, particularly for protocols entailing medication washout and/or placebo treatment. The majority of psychiatric patients who are asked to participate in clinical trials have adequate capacity to provide consent. Thus, in a study specifically designed to examine the capacity of schizophrenic patients to give informed consent, cognitive dysfunction and negative symptoms (apathy and avolition). but not psychotic symptoms (hallucinations, delusions), were found to be associated with impaired decisional capacity (Moser et al., 2002). These features are probably not unique to schizophrenia but are likely to apply to many other forms of illness. 

Another important aspect to this question is the cognitive dysfunction associated with severe depression. Much of the memory effects are focused on events occurring during the illness and the period of treatment [see Abrams ( 94) for a detailed analysis]. Thus, many depressed patients may suffer from severe memory disturbances before their course of ECT, and paradoxically appear to improve over a course of treatment. Thus, improvement in the attention and concentration disruption often associated with severe depression is so significant, that it overrides the organic amnesia induced by the course of seizures. 

Friedman JI, Adler DN, Davis KL (1999) The role of norepinephrine in the pathophysiology of cognitive disorders potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer s disease. Biol. Psychiatry 46 1243-1252. 

Overall, in relatively young and healthy patients, the cumulative risk of contracting TD when exposed to neuroleptics ranges from 4% to 7% per year during the first several years of treatment. Approximately one-third of the patients will develop this largely irreversible disorder within the first 5 years of treatment. This represents an astronomical risk for patients and should become part of the awareness of all mental health professionals, their patients, and their patients families. Furthermore, we shall find that TD brings with it the additional risk of irreversible cognitive dysfunction and dementia (chapter 5). 

Schizophrenia is a severe mental disorder associated with both a specific profile of symptoms and a complex pattern of neurocognitive dysfunction. The first effective treatment for schizophrenia was discovered fortuitously in the mid-1950s (Delay and Deniker, 1955) and subsequently shown in the mid-1970s to mediate their effects at dopamine D2 receptors (Seeman and Lee, 1975 Wong et al., 1986). The dopamine hypothesis has been the dominant neurochemical model of schizophrenia (Carlsson, 1988) and has proved heuristically valuable since that time. For example, all current treatments for schizophrenia mediate their effects via a blockade of the dopamine (D2) receptor. Further, certain forms of cognitive dysfunction may relate to impaired dopaminergic function within the prefrontal cortex (see Chapter 1.1 this volume). Nevertheless, over recent years, limitations of the dopamine hypothesis have become increasingly apparent, as has the need for alternative neurochemical conceptualizations of schizophrenia. 

In studies of the neurotoxic effects of low-dose methotrexate treatment, dizziness, headache, visual disturbances or hallucinations, lack of concentration, cognitive dysfunction, and depression-like symptoms were detected in 1-35% of patients (527,528). Advanced age and mild renal insufficiency were possible susceptibility factors (529). 

Scheibel RS, Valentine AD, O Brien S, Meyers CA. Cognitive dysfunction and depression during treatment with interferon-alpha and chemotherapy. J Neuropsychiatry Clin Neurosci 2004 16 185-91. 

The most important excitatory neurotransmitter in the central nervous system (CNS) is glutamate, reported to regulate Ca " accumulation through excessive activation of NMDA receptors. Memantine is an NMDA antagonist that has been used to treat neurological syndromes and cognitive dysfunction (Farlow et al., 2003). A small beneficial effect of memantine was observed at six months of treatment in moderate to severe AD (Areosa et al, 2005). 

Specificaiiy, may be usefui for treatment of cognitive dysfunction and fatigue as residuai symptoms of major depressive disorder unresponsive to muitipie prior treatments... 

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