Table 6.
Gastrointestinal adverse effects in relation to CLOZAPINE blood levels.
| Reference | Type of Study | Age (Mean) (Years) |
Comedication | Averaged Serum Levels of Clozapine (ng/mL) |
Duration | Reported Side Effects |
Correlation to Clozapine Plasma Levels | Jadad Score |
|---|---|---|---|---|---|---|---|---|
| [41] | Cross-sectional | 36.6 ± 9.1 (range 20–54) | Benzodiazepines, lithium, antidepressants, other medically indicated agents |
Median 291, range: 15–726 | 2.15 ± 2.30 years | Nocturnal sialorrhea, drooling, parotid swelling, constipation | No | 0 |
| [46] | Prospective, observational follow-up | 19–65 | Benzodiazepines | CLOZ: 385 ± 183 (range 147–974) NCLOZ: 174 ± 84 (range: 43–445) |
12 weeks | Hypersalivation, constipation | No | 1 |
| [52] | Prospective | CLOZAPINE subsample: 31.37 ± 11.8 | Not reported | 165.4 ± 163.4 | 18 weeks | Pathologic liver function tests (LFTs): SGOT, SGPT, GGT, ALP, bilirubin | Yes, for SGPT only | 0 |
| [35] | Cross-sectional, naturalistic | Range 22–55 | Nortriptyline, levomepromazine, clonazepam, hyoscyamine, oxazepam, chlorprothixene, phenobarbital, nitrazepam, biperiden, orphenadrine, benztropine, diazepam, piroxicam, disulfiram | Median: 1076 (range 706–1882) NCLOZ/CLOZ ratio: 0.77 ± 0.17 |
Median: 2.5 (range 1.0–9.0) years | Increased liver enzyme activity (increased GGT, ALP, AST, ALT) | No | 0 |
| [77] | Cross-sectional, controlled | Patients: 40.94 ± 10.15 Controls: 40.09 ± 1.67 |
Not reported | 594.90 ± 492.90 220.33 ± 182.55 |
At least 4 months | AST, ALT | No | |
| [65] | Cross-sectional | 38.2 ± 11.3 (range 22–74); Caucasians: 40.2 ± 8.6, Asians: 36.3 ± 13.4 | Not reported | Caucasians: 415.3 ± 185.8, Asians: 417.1 ± 290.8 | ≥6 months | Elevated levels of alanine (ALT) and aspartate (AST) transferases | No | 0 |
| [43] | Open-label trial | 13.3 ± 2.7 (range 9–16) | No | 289 ± 116 | 6 weeks | Increased hepatic transaminase | No | 0 |
| [40] | Data from double-blind and open-label clozapine trials | 13.5 ± 2.5 (range 7.0–19.1) | Not reported | 455.6 ± 285.1 (n = 46) | 6 weeks | Elevated liver enzymes (AST, ALP, ALT) | No | 0 |
| [53] | Cross-sectional | 39.3 ± 9.8 (range 20–61) (CLOZAPINE group: 37 ± 8.2, NON CLOZAPINE group: |
Laxatives (laxsol, polyethylene glycol, lactulose), antipsychotics (risperidone, aripiprazole, haloperidol, amisulpride, aripiprazole + quetiapine) omeprazole, metformin, cholecalciferol |
489 ± 137 (range 284–885) | At least 3 months | Colonic hypomotility | Positive correlation Clear colonic hypomotility in 80% of CLOZAPINE patients, with Colonic Transit Time (CCT) four times longer than population morms (p < 0.0001) and NON-CLOZAPINE patients (p < 0.0001) |
0 |
| [54] | Retrospective, collection of records | Males: 43.5 ± 10.1 Females: 47.2 ± 11.2 |
Anticholinergic agents | CLOZ: Laxative users: 533 ± 0.29 Non-laxative users: 486 ± 30 NCLOZ: Laxative users: 337 ± 0.19 Non-laxative users: 269 ± 0.18 |
>3 months | Constipation | NCLOZ vs. laxative use, p = 0.046) | 0 |