d-Cycloserine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label study

Abstract

D-cycloserine, a partial agonist at the strychnine-insensitive glycine site of the NMDA receptor complex, was tested as adjuvant treatment to conventional neuroleptics in chronic schizophrenic volunteers. The drug was administered, o.a.d., at the daily dose of 250 mg for six weeks. Mental status outcome measures were completed at the end of each week of treatment. The major finding was a deterioration of the patients' clinical condition, specifically of their psychotic symptoms. These preliminary results are discussed among others in view of d-cycloserine pharmacologic properties and recent findings on the interaction between NMDA agonists and dopamine system. This study, finally, suggests the need for a controlled dose-finding trial to establish the activity and a therapeutic "window" of this drug in schizophrenia.

D-Cycloserine Increases Positive Symptoms in Chronic Schizophrenic Patients When Administered in Addition to Antipsychotics A Double-Blind, Parallel, Placebo-Controlled Study

“…We found that D-cycloserine exacerbated psychotic symptoms in schizophrenia at blood levels 15 times lower (i.e., between 2.0 and 2.9 microgram/ml). The second study reported that 250 mg D-cycloserine daily in addition to conventional antipsychotics aggravated psychotic symptoms in four of seven patients with chronic schizophrenia (Cascella et al 1994). Comparison of this study with our previous report (van Berckel et al 1996) and the only other report currently available in which beneficial effects of D-cycloserine on the negative symptoms of schizophrenia were described (Goff et al 1996) is hampered by differences in design (increasing dosages versus fixed dose), treatment regime (drug-free patients versus patients treated with neuroleptics), and inclusion criteria.…”

“…Similarly when D-cycloserine was added to clozapine in dosages of 5 mg, 15 mg, 50 mg, and 250 mg consecutively for 2 weeks no changes were found (Goff et al 1996). Interestingly, 250 mg D-cycloserine daily, in addition to typical antipsychotics, was found to exacerbate psychotic symptoms, such as hallucinations, conceptual disorganization, and aggressive behavior in four of seven schizophrenic patients, although one patient with predominantly negative symptoms showed some improvement (Cascella et al 1994). Moreover, the treatment of 10 psychotic patients with D-cycloserine in dosages between 500 mg and 3000 mg daily induced an exacerbation of hallucinations and paranoia in seven patients (Simeon et al 1970).…”

Homer 1a Gene Expression Modulation by Antipsychotic Drugs Involvement of the Glutamate Metabotropic System and Effects of D-Cycloserine

“…In contrast, it has been shown that at doses of 100 mg/day or 250 mg/day D-cycloserine had no effect on negative symptoms and worsened positive symptoms of psychosis. This may be explained by the evidence that at higher concentrations D-cycloserine acts as an antagonist rather than a partial agonist at the glycine site (Cascella et al 1994;van Berckel et al 1999). Finally, it has been suggested that glycine may be less effective when combined to clozapine than when combined to conventional neuroleptics (Evins et al 2000).…”

Treatment of Comorbid Tuberculosis and Depression

“…41 Preliminary evidence has indicated that the appropriate dose of cycloserine for the treatment of schizophrenia is in the range of 50 to 100 mg/day. [40][41][42] Larger doses of 250 mg/day and 1 g/day have been associated with anxiety, irritability, and depression. 43,44 Cycloserine may be contraindicated in combination with clozapine.…”