Table 1.
Randomised controlled studies comparing medication discontinuation with maintenance treatment for the prevention of relapse in first episode schizophrenia
| Study (location) |
Number of participants |
Diagnosis | Study design |
Remission duration |
Intervention group |
Control group |
Relapse definition | Follow-up duration after discontinuation |
Relapse rate |
Hospital admission rate |
|---|---|---|---|---|---|---|---|---|---|---|
| Kane et al, 198227 (USA) | 28; MT = 11 PL = 17 |
S (RDC), unspecified psychosis, other psychiatric disorder, manic disorder with schizotypal features | RCT (double-blind) | At least 4 weeks stable remission | Placebo | Fluphenazine hydrochloride (5–20 mg/day), fluphenazine decanoate i.m. (12.5–50 mg every 2 weeks) | Substantial clinical deterioration with a potential for marked social impairment | 1 year | 41 v. 0% | |
| Crow et al, 198628 (UK) | 120; MT = 54 PL = 66 |
Schizophrenic illness (PSE) | RCT (double-blind) | 30 days discharge status | Placebo | Flupenthixol i.m. (40 mg/month), chlorpromazine (200 mg), haloperidol (3 mg), pimozide (4 mg), trifluoperazine (5 mg) | Readmission to psychiatric care for any reason, readmission considered necessary by the clinicians responsible but for some reason not possible (e.g. lack of beds, refusal of patient), active antipsychotic medication considered by the clinician to have become essential because of features of imminent relapse | 2 years | 62 v. 46% (raw score) | |
| McCreadie et al, 198929 (UK) | 15; MT = 8 PL = 7 |
S (clinical) | RCT (double-blind) | 1 year relapse free on treatment | Placebo | Pimozide or flupenthixol i.m. | Hospital admission | 1 year | 57 v. 0% | |
| Gaebel et al, 200223 (Germany) | 115; MT = 36 PI = 39 CI = 40; patients who could be discontinued: PI = 31 CI = 32 |
S (ICD-9 (1978) and RDC) | RCT (open) | Stable clinical condition for at least 3 months | Targeted discontinuation:
|
Standard treatment (at least 100 mg chlorpromazine equivalents per day) | Psychotic deterioration of maximum intensity usually demanding hospital admission and minimum change score on the BPRS psychotic factor ≥10, GAS ≤ 20 and CGI ≥ 6 | 2 years | MT: 38% PI: 42% CI: 67% |
31 v. 38% |
| Chen et al, 201030 (Hong Kong) | 178; MT = 89 PL = 89 |
S, SCP, SCA, brief psychotic disorder NOS (DSM-IV, 1994) | RCT (double-blind) | 1 year relapse free on treatment | Placebo | 400 mg quetiapine | Reappearance of definite psychotic symptoms (beyond thresholds on PANNS subscales 3–5) and CGI severity ≥3 | 1 year | 63 v. 30% (raw score) | 16 v. 6% |
| Boonstra et al, 201131 (Netherlands) | 20; MT = 9 DS = 11 |
S, SCP, SCA (SCID-IV) | RCT (open) | 1 year in remission | Medication discontinuation | Medication continuation for a minimum of 6 months | ≥4 any PANSS core item and 20% increase in total PANSS or admission to hospital | 2 years | 91 v. 45% (Kaplan–Meier) | 36 v. 12% |
| Gaebel et al, 20119 (Germany) | 44; MT = 23 DS = 21 |
S, SCP (clinical ICD-10, 1992) | RCT (open) | 1 year relapse free on treatment | Targeted discontinuation: intermittent treatment | Risperidone or haloperidol continuation (2–8 mg) | PANSS positive change >10, CGI change ≥6 and GAF decrease >20 | 1 year | 19 v. 0% | 19 v. 0% |
MT, maintenance treatment; PL, placebo; S, schizophrenia; RDC, research diagnostic criteria; RCT, randomised controlled trial; PSE, present state examination; i.m., intramuscular; PI, prodrome based intervention; CI, crisis intervention; BPRS, brief psychiatric rating scale; GAS, global assessment scale; CGI, clinical global impression; SCP, schizophreniform psychosis; SCA, schizoaffective psychosis; NOS, not otherwise specified; DS, discontinuation strategy; PANSS, positive and negative syndrome scale; SCID-IV, Structured Clinical Interview for DSM-IV.