Catecholaminergic Drugs in Chronic Schizophrenia

Abstract

The effect of dopaminergic-related and stimulatory drugs have been studied in chronic hebephrenic schizophrenics untreated with neuroleptic drugs. 6 patients received therapy of 2 g L-dopa + 200 mg carbodopa per day orally for 30 days, then placebo for 30 days. Following that 3 of the same patients received therapy of 2 g L-dopa + 200 mg carbodopa + 300 mg imipramine orally for 30 days, then placebo for 30 days. Following that the same 3 patients recieved 1 mg apomorphine s.c. for 15 days, then placebo for 15 days, then 1 mg apomorphine s.c. + 2 g L-dopa + 200 mg carbodopa per os daily for 15 days, then placebo for 15 days. The patients were examined psychologically by the Wittenborn Rating Scale, the Weigl Object-Sorting Test, and tests for verbal learning and verbal association, before and after each therapeutic trial. Levels of FSH, LH, testosterone and GH were assayed radioimmunologically before, in the middle of and after each course of therapy. 2 patients showed improvement in the affective-behavioural symptomatology during therapy, while the other 4, who had a more severe degree of mental deterioration and destruction, were unchanged. FSH and LH levels, very low under basal conditions, did not change under therapy. Testosterone was very low before therapy and increased in only 1 subject. Normal basal GH levels increased during therapy in some of the patients, but not constantly. The results obtained are discussed in relation to the catecholamine hypotheses of schizophrenia.

Treatment of the Neuroleptic-Nonresponsive Schizophrenic Patient

“…These studies have been reviewed by us elsewhere (Meltzer et al 1986) and by Christison and colleagues (1991). L-dopa and d- amphetamine act mainly to increase dopaminergic activity and may be of benefit, especially in patients with marked negative symptoms and few positive symptoms (Inanaga et al 1972; Gerlach and Luhdorf 1975; Brambilla et al 1979; Cesarec and Nyman 1985). Exacerbations of positive symptoms may occur in some patients (Yaryura-Tobias et al 1970; Angrist et al 1973; Calil et al 1977).…”

The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia

“…For example, a number of studies suggest that amphetamine may induce psychotic states that in some respects resemble schizophrenia (Connell, 1958;Ellinwood, 1967;Angrist and Gershon, 1970;Snyder, 1977) and worsen psychotic symptoms in patients with preexisting schizophrenia (Casey et al, 196 1;Chiarello and Cole, 1987, forreview). Paradoxically, however, there have been reports of efficacy of centrally active dopamine agonists in alleviating both positive symptoms (i.e., hallucinations, excitement, delusions) and, to a greater extent, so-called negative or defect symptoms (i.e., emotional blunting, anergy, anhedonia, amotivation, social withdrawal) in schizophrenia (Inanaga et al, 1972(Inanaga et al, , 1975Buchanan et al, 1975;Gerlach and Luhdorf, 1975;Ogura et al, 1976;Brambilla et al, 1979;Alpert and Rush, 1983;Kay et al, 1985-86;Opler et al, 1985). In the present study, patients with schizophrenia were treated simultaneously with (1) an antipsychotic (i.e., haloperidol) that has a relatively high affinity for blockade of subcortical D, receptors (Andersen et al, 1986;Tamminga and Gerlach, 1987), which are thought to be important in mediating positive psychotic symptoms, and (2) amphetamine, which in the presence of haloperidol would be expected to stimulate preferentially D, receptors.…”

A meta-analysis of the response to chronic l-dopa in patients with schizophrenia: therapeutic and heuristic implications

“…Over a 10-month period, the general estimated prevalence of exacerbation in schizophrenia is 16% in APD-treated individuals but 56% in patients who are not taking APDs (Gilbert et al 1995). The majority (84%) of patients in the current review who received l-dopa without concomitant APDs did so for less than 4 weeks Alpert et al 1978;Brambilla et al 1979;Beramendi et al 1980;Davidson et al 1987). Furthermore, insofar as l-dopa increases verbal communicativeness (Yaryura-Tobias et al 1971), rating scales that depend on self-reporting of symptoms may overestimate the emergence of psychotic symptoms in the previously withdrawn patient.…”

“…2); all three studies in which over 20% of patients worsened (Yaryura-Tobias et al 1970a, 1970bCalil et al 1977) had very small patient samples (n 4). A total of 64 patients in five studies received l-dopa without concomitant APDs; 38% of the latter showed definite worsening Alpert et al 1978;Brambilla et al 1979;Beramendi et al 1980, Davidson et al 1987. Inanaga et al (1975a) 0.2722 0.1670 Asano et al (1973) 3.6129 0.0000 Fleming et al (1970) 1.6000 0.0774 Gerlach and Luhdorf (1975) 0.8275 0.0366 Overall 0.7116 0.0000…”

“…While 38% of the pool of all APDfree patients treated with l-dopa had definite clinical worsening, the latter is mitigated by several considerations. All those patients received high doses (>1000 mg/ day) of l-dopa, often after abrupt cessation of APDs Alpert et al 1978;Brambilla et al 1979;Beramendi et al 1980, Davidson et al 1987). Schizophrenia and particularly untreated schizophrenia are per se associated with an increased risk of exacerbation.…”