Long-term neuroleptic treatment of chronic schizophrenic patients: Clinical and biochemical effects of withdrawal

Abstract

In 17 chronic schizophrenic patients under chronic neuroleptic treatment for 13 years, a 30-day drug withdrawal resulted in early relapse of four patients, slight deterioration in five, and slight amelioration in eight patients. No incidence of neuroleptic symptoms such as tardive dyskinesia occurred. Prolactin in plasma and cerebrospinal fluid (CSF), not being elevated under chronic treatment, decreased significantly after 30 days of withdrawal. Homovanillic acid and 3-methoxy-4-hydroxyphenylglycol in CSF ranged normally and did not change during withdrawal. In contrast, plasma noradrenaline was elevated and decreased after drug discontinuation. No unequivocal relationship between biochemical and psychopathological features was found.

Suspension Therapy in Acute Schizophrenia

“…Analysis of uri nary catecholamines is a reliable means of assessing sym pathoadrenal function in schizophrenic patients [37], We recorded a decrease in urinary epinephrine and norepi nephrine excretion during the therapeutic suspension phase, primarily in cases where baseline values under the preceding haloperidol intake had been elevated. After long-term neuroleptic intake, too, serum norepinephrine levels fell only if the respective values before discontinua tion had been distinctly elevated [4,25], A significant decrease in VMA -the main metabolite of norepineph rine and representative of the norepinephrine metabolism [38] -after discontinuation of neuroleptic therapy was also detected in our study only if baseline values were ele vated.…”

“…Data on the predic tive value of serum prolactin for the clinical effect of sub sequent neuroleptic withdrawal in chronic schizophrenic patients are divergent: Some authors [5,25,[29][30][31] found no statistically significant correlation between prolactin levels and psychopathological changes after neuroleptic withdrawal. In contrast, others [4,6,32,33] reported that patients with an unfavorable withdrawal effect (rapid relapse) have lower baseline prolactin levels than patients with a more favorable withdrawal effect. It is concluded from these data that the dopamine-blocking effect of neu roleptics is less marked, at least functionally, in these patients than in patients with a more favorable withdraw al effect, i.e.…”

“…The serum pro lactin values, which had been elevated under neurolep tics, were rapidly restored to baseline values within 48-72 h (according to our data within 3-7 days). As expected, prolactin levels also decrease after withdrawal of long term neuroleptic medication in chronic schizophrenia [4,5,25]. Green et al [26] showed that the course of prolac tin values differed substantially in patients with previous ly high and low prolactin levels after withdrawal: only if baseline values were low did prolactin levels rise in the neuroleptic-free interval after an initially rapid fall from the 2nd weeks onwards [V-shaped course, cf.…”

“…A number of reports are available on neuroleptic with drawal in chronic schizophrenia [1][2][3][4][5][6][7]. These studies are focused primarily on the question of what psychopathological changes occur after discontinuation of pharmaco therapy and whether they are associated with any neu roendocrine and biochemical changes (for details see dis cussion).…”

Methylphenidate Response, Psychopathology and Tardive Dyskinesia as Predictors of Relapse in Schizophrenia

“…The most promising of these are measures of central nervous system (CNS) dopamine (DA) activ ity including plasma prolactin levels (PRL) (Brown et al 1981;Zander et al 1981;Wistedt et al 1982;Lieber man et al 1986a), growth hormone response to DA agonist stimulation (Cleghorn et al 1983;Mueller Spahn et al 1984;Lieberman et al 1986), plasma neu roleptic levels (Brown et al 1982;Brown et al 1985;Marder et al 1987), pHV A (Davidson et al 1991) and behavioral response to DA agonist stimulation (van Kammen et al 1982;Davidson et al 1987;Lieberman et al 1987b;Angrist et al 1981). The latter line of inves tigation is based on the fi.nding originally demonstrated by Janowsky et al (1973) and Angrist et al (1980) that a single or brief administration of a DA agonist can in duce psychotic symptoms in schizophrenics in doses that would not induce psychosis in normal subjects (Lie berman et al 1987a).…”