Eighty-one applicants consented to participate in the study, of whom 9 did not appear at the first clinic visit. The remaining 72 subjects were randomly assigned and received the first dose of CBZ or placebo. Ten subjects started treatment but discontinued their participation before completing one week of treatment (none of them reported side-effects). The 19 non-evaluable patients did not differ significantly from the 62 evaluable ones on any of the intake characteristics (data not shown).
Results from the 62 subjects (CBZ, n = 28; placebo, n = 34) who received medication for 1 week or more showed no significant differences in socio-demographic characteristics, drug use history, or psychiatric co-morbidity between the CBZ and placebo groups (). The most frequent psychiatric disorders were antisocial personality (n = 18), phobic disorders (n = 16), and post-traumatic stress disorder (n = 8).
Socio-demographic characteristics and drug use history of patients on medication ≥ 1 week
All patients attended most of the scheduled standardized individual counseling sessions during the time they participated in treatment. Bi-weekly CBZ plasma level monitoring showed a mean (S.D.) CBZ plasma level of 3.63 (2.52) μg/ml during week 2, 5.61 (3.54) μg/ml during week 4, and 3.57 (2.57) μg/ml during week 6 of treatment. There was no difference (χ2 = 0.653, df = 1) between the number of patients in either group who reported at the exit interview that they thought they had received a particular treatment.
Mean (S.D.) retention time in the study was 30.6 (18.2) days. This estimate of retention time in the study is necessarily biased since it excludes patients participating less than one week and the maximum retention time of 8 weeks was fixed by the study design. There were no significant differences between the two groups for retention rates χ2 = 0.27, P = 0.60) or for the number of patients who completed the 8-week study (χ2 = 0.2, P = 0.65) (). For all subjects as a whole, there were significant decreases between intake and treatment termination in the self-reported drug outcome variables, including cocaine use in grams (F = 8.79; df = 1,58; p = < 0.005) and dollars spent (F = 8.18; df = 1,59; P = < 0.006) in the past 24 h, and cocaine craving (F = 9.08; df = 1,48; P < 0.005). However, these decreases were not associated with significant decreases in the percentage of urines negative for cocaine (F = 0.44; df = 1,60; p = 0.51) ().
There were no significant differences between CBZ (■, n = 28) and placebo (○, n = 34) for retention in treatment for cocaine dependence (62 patients completing one week of treatment).
Mean (SE) percentage of urines negative for cocaine at week 1 of and discharge from (End Tx) treatment. There were no significant differences between CBZ (■, n = 28) and placebo (□, n = 34).
For the 62 evaluable subjects, the first method of analysis (comparing pre-treatment versus post-treatment) showed no significant differences between CBZ and placebo on self-reported cocaine used in grams (F = 2.44; df = 1,58; P = 0.12) or dollars (F = 2.54; df = 1,59; P = 0.12), self-reported cocaine craving (F= 0.4; df = 1,48; P = 0.5) or percentage of urines negative for cocaine (F = 2.01; df= 1,60; P = 0.16). There were no significant group by time interactions for self-reported cocaine use in grams (F = 1.57; df = 1,58; P = 0.22) or dollars (F = 1.37; df = 1,59; P = 0.25), self- reported cocaine craving (F = 0.40; df = 1,48; P = 0.52), or percent of urines negative for cocaine(F = 0.44; df = 1,60; P = 0.51).
During the 8 weeks of treatment, there was a significant decrease in BDI (F = 21.7; df = 1,48; P < 0.0001) and SCL-90R total (F= 31.14; df = 1,56; P < 0.0001) scores for both groups, with no significant differences between CBZ and placebo groups (F = 0.4; df = 1,48; P = 0.53; and F = 0.16; df = 1,56; P = 0.69 respectively) (data not shown). There were no significant group by time interactions for the BDI (F = 0; df = 1,48; P = 0.98) or SCL-90R scores (F =0.57; df = 1,56; P = 0.45).
The second method of analysis (comparing CBZ and placebo groups stratified by urine toxicology result for cocaine on the first day of treatment), showed no significant differences between the CBZ and placebo groups for retention in treatment, urine toxicology results, or cocaine use as measured by amount in grams or money spent.
Post hoc weekly comparisons using the third method of analysis (remaining subjects at each timepoint) showed that the only significant group difference (Fisher’s exact test, P < 0.01) was lower self-reported weekly cocaine craving in the MCCS for the CBZ group at week 5. There were no other significant treatment outcome differences between CBZ and placebo (data not shown). The sample of 19 completers showed no significant differences between CBZ and placebo groups on any outcome measure (data not shown).
None of the patients treated with CBZ had severe or medically serious side-effects. Ten (16.1%) patients had mild or moderate side-effects. The most frequent (10%) was increased blood pressure. There were no significant differences between CBZ and placebo groups for frequency or severity of symptoms (Fisher’s exact test = 0.47). CBZ was discontinued in 3 patients due to side-effects (2 patients had high blood pressure and 1 had skin rash and leukopenia); these patients continued receiving counseling for the remainder of the 8-week trial. All side-effects resolved without hospitalization or permanent sequelae.