Subject positive symptoms

Controlled clinical investigations with careful titration of doses in normal subjects demonstrate that ketamine produces negative symptoms, such as withdrawal and the subtle cognitive impairments associated with schizophrenia [25]. As is the case for schizophrenia, these symptoms occur without clouding of consciousness or frank dementia. Positive symptoms with auditory hallucinations and fully... 

Because the reduction in metabolism in the medial frontal cortex produced by risperidone is associated with alleviation of positive symptoms in patients with schizophrenia, the observation of a reduction in metabolism at a similar site in healthy subjects supports the hypothesis that the antipsychotic effect of risperidone arises, at least in part, from a physiologic effect that occurs in both patients with schizophrenia and healthy subjects. 

It is unquestionable that current antipsychotic therapy is comparatively effective and at the same time disappointingly insufficient. These drugs can treat the symptoms of the disorder but certainly do not provide a cure. The great majority of patients will have between 20 and 50% reduction in symptom severity. Some will have marked improvement beyond these figures, although this is rare, and a small minority of patients will be entirely refractory to all forms of treatment currently available. Full results from antipsychotic therapy take considerable time (although initial effects on some positive symptoms can be seen in a few days). Whereas the effect of benzodiazepines on anxiety and sleep can be measured in hours, and that of antidepressants in weeks, the full impact of antipsychotic therapy is measured in months. A study by Robinson et al. (1999) showed that only 20% of patients responded after 4 weeks of treatment with conventional antipsychotics, whereas after 26 weeks the number of responders had grown to about 70%. Similar results were reported with clozapine treatment, where a response was observed in 40% of subjects after 4 weeks and in 60% of subjects by week 17 (Kane et al., 2001). Clinical observations clearly show that improvement in... 

Figure 3.3 Dopamine transmission and schizophrenia. This graph illustrates the effect of amphetamine (0.3 mg/kg) on f IJIBZM binding in healthy control subjects and untreated patients with schizophrenia. The results indicate that when challenged with amphetamine, patients with schizophrenia release more dopamine than healthy controls. The amount of release is related to the increase in positive symptoms. Source ...

The diagnosis of schizophrenia is subjective, based on three types of symptoms (1) positive, (2) disorganized, and (3) negative. Positive symptoms include delusions and... 

Only two randomized, controlled trials have been completed, and neither provides anything like compelling data (Table 2.6). Chouinard and Albright (1997) conducted a unique evaluation of a subset of patients from a previously conducted clinical trial. Subjects were categorized and profiled at baseline and end point according to clinical severity, and a group of psychiatric nurses were asked to rate various aspects of likely outcome and quality of life to each profile (mild, moderate or severe symptoms). Health state utilities were then calculated risperidone was found to provide more than double the number of quality-adjusted life years compared with haloperidol. Csernansky and Okamoto (1999) conducted a rather more conventional trial, but included no economic analyses. However, they did find that the use of risperidone substantially reduced relapse rates compared with haloperidol—an outcome likely to have a positive impact on cost-effectiveness. 

Moreover, experimental studies are often inconclusive. Rarely does the antidepressant medication far exceed the placebo in effectiveness, and sometimes subjects in the control group actually report greater symptom relief Equally important, the newer classes of antidepressant medications (the SSRIs), hyped as the latest wonder drugs, are actually no more effective than categories of medications (for example, tricyclic antidepressants) that were discovered in the late I950s. Finally, these studies have no way to assess whether medications work better than positive life changes. The sociologist Allan Horwitz asks ... 

In a recent report, the mean CY-BOCS score at initial assessment (23 6.5) did not differ between child and adolescent OCD subjects. It should be noted that although the CY-BOCS is an anchored ordinal scale, it is not linear and lacks sensitivity to change when symptoms are severely impairing. For example, time occupied is scored as 4 when more than 8 hours/day are spent in either obsessions or compulsions, while 4 hours/day would rate a score of 3—i.e., a 50% decrease in time lowers this item score by one point (out of 5 ordinal scores). It is for this reason that a decrease in CY-BOCS score of more than 25% is considered clinically significant improvement and a number of controlled studies have used a 25% reduction to define a positive response. The CY-BOCS remains the gold standard for both baseline evaluation as well as for monitoring effects of treatment. 

Treatment of the comorbid patient presents a number of challenges (Fig. 39.2). The phenotype of OCD and Tourette s disorder (TD) is encountered frequently as there is a bidirectional overlap between the two conditions. In a review of 11 clinical studies, TD was found in an average of 21% of juvenile OCD subjects (Geller et ah, 1998). These subjects are more often male with an earlier age at onset and positive family history of OCD and tics. Kurlan et al. (1993) suggested that obsessional symptoms might respond less well to the SSRIs in these subjects. 

Pemoline (Cylert), (112.5 to 185.5 mg) was assessed in a 3-week open trial in 15 adolescents with CD, ADHD, and SUD (Riggs et ah, 1996). Three of the subjects were receiving other psychotropic medications (clonidine (Catapres) and paroxetine [Paxil]). All subjects had a significant improvement in ADHD symptoms (p <0.002) while 10/13 reported that the pemoline (Cylert) assisted in their substance rehabilitation. No subjects developed a significant elevation in their liver function tests, nor did any subjects test positive for substances of abuse for the duration of the study. No interactions between pemoline (Cylert) and any substances of abuse were reported. 

Paroxetine. Paroxetine, also a serotonin reuptake inhibitor, has been the subject of a case report in two subjects. Ringold [1994] reported the effective treatment of two individuals who had not responded to prior therapy with fluoxetine and sertraline. Both individuals had comorbid psychiatric problems. Subject A demonstrated both social phobia and dysthymia. Although her symptoms of dysthymia were clinically responsive to fluoxetine therapy, her social phobia symptoms were resistant. Subject B had body dysmorphic disorder, obsessive-compulsive disorder, and social phobia. His obsessive-compulsive disorder symptoms benefited from fluoxetine therapy, but his social anxiety was resistant. Sertraline therapy was attempted in both subjects. Subject A required discontinuation because of adverse effects. Subject B experienced a worsening of both obsessive-compulsive disorder and social phobia symptoms. Both subjects demonstrated a positive response in their symptoms when switched to paroxetine [20 mg/day]. 

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