Table 4.
Evidence table on interventions to improve medication adherence.
| Intervention type | Study | Study type | Sample characteristics | Cases | Duration of study | Adherence measure | Effect on adherence | Effect other outcome measures | RoB |
|---|---|---|---|---|---|---|---|---|---|
| Behavioral—adherence therapy | Anderson et al. (2010) | RCT, SB | Mixed (%FEP NR); stable; SZ + SZA | 12 intervention vs. 14 TAU | 8 w | PETiT | t = 1.20, n.s. | Low | |
| Chien et al. (2015) | RCT, SB | Mixed (%FEP NR); stable; PSD | 57 intervention vs. 57 TAU | 4 m; FU at 6 m | ARS | F = 7.45, p = 0.007; ES = 0.72 | PANSS score (F = 7.32, p = 0.008); positive symptoms score (F = 7.28, p = 0.008); negative symptoms score (F = 7.81, p = 0.006); ES = 0.70–0.75; number of rehospitalizations (F = 5.01, p = 0.030), ES = 0.48; insight into illness and/or treatment (F = 6.58, p = 0.021), ES = 0.51; functioning (F = 6.89, p = 0.014), ES = 0.68 | Low | |
| Chien et al. (2016) | RCT, SB | Mixed (%FEP NR); stable; PSD | 67 intervention vs. 67 TAU | 12 w; 18 m FU (2w, 6m, 18m) | ARS | Non-adherent: 85 vs. 90% (F = 9.10, p = 0.005), effect size = 0.30 | Insight (F = 10.98, p = 0.001), ES = 0.40; functioning (F = 8.90, p = 0.005), ES = 0.29; symptom severity (PANSS) (F = 10.10, p = 0.003), ES = 0.32, hospital rate duration (F = 8.80, p = 0.005), ES = 0.28; hospital rate frequency (F = 3.47, p = 0.092) | Low | |
| Gray et al. (2006) | RCT, SB | Chronic; state NR; SZ | 204 intervention vs. 205 HE (control) | 52 w (8 weekly sessions within first 5 m) | MAQ, SAI-C | MAQ: n.s.; SAI-C: -n.s. | n.s. QoL and BPRS | Low | |
| Schulz et al. (2013) | RCT, SB | Mixed (%FEP NR); acute; SZ | 80 intervention vs. 57 TAU | 12 w | CDR, MARS | CDR: F = 2.29, n.s.; MARS: difference 0 | PANSS (F = 6.19, p < 0.05); beliefs about treatment (DAI) n.s.; GAF n.s. | Low | |
| Behavioral—CBT | Bechdolf et al. (2010) | RCT, SB | Mixed (% FEP NR); acute; PSD | 16 CBT vs. 27 PE | 8 w, results FU at 24 m | 4-point rating scale | F = 1.31, p = 0.26 | Rehospitalization rate 37.5% vs. 59.3%, (χ2 = 2.50, n.s.); symptom severity n.s. | Low |
| Behavioral—cognitive adaptation training | Velligan et al. (2008) | RCT, SB | Chronic; stable; SZ + SZA | 34 CAT vs. 32 PharmCAT vs. 29 TAU | 9 + 6 m FU (3 and 6 m) | Unannounced in-home pill counts; prescription refill rates | Pill count adherence: CAT vs. TAU ES = 1.09; Pharm-CAT vs. TAU ES = 1.05; prescription refill rates: main effect of group (F = 3.93, p < 0.020), CAT vs. TAU (F = −2.85, p < 0.006), Pharm-CAT vs. TAU n.s.; CAT vs. TAU ES = 0.51 and Pharm-CAT vs. TAU ES = 0.33 | Symptom severity n.s.; relapse rate CAT vs. TAU (χ2 = 8.29, p < 0.004); Pharm-CAT vs. TAU (χ2 = 8.20, p < 0.005); relapse in 15 m >65% CAT and Pharm-CAT vs. 19% TAU; functional outcome CAT vs. TAU 6 m treatment ES = 1.47 and 6 m FU ES = 0.50, Pharm-CAT vs. TAU at 3 m ES = 0.42, at 6 m treatment ES = 0.44, at 6 m FU ES = 0.22 | Low |
| Velligan et al. (2013) | RCT, SB | Chronic; stable; SZ + SZA | 46 MeM vs. 46 PharmCAT vs. 45 TAU | 9 m | Electronic monitor, pill counts | e-monitoring: treatment group effect F = 47.29, p < 0.0001; effects for time F = 0.06, n.s.; time × group effect F = 0.44, n.s.; PharmCAT vs. TAU ES = 1.03 and MeM vs. TAU ES = 0.98. Pill counts: significant main effect of group F = 7.83, p < 0.0001 and n.s. effects of time F = <1, n.s.; time × group interaction F = 2.34, p = 0.06; adherence rate PharmCAT 91% vs. MeM 86%, t = 2.05, p = 0.04; PHARMCAT 91% vs. TAU 80%, t = 3.95, p = 0.0001; MeM 86% vs. TAU 80%, t = 1.82, n.s. | Symptom severity and functioning (all n.s.) | Low | |
| Family therapy | Kopelowicz et al. (2012) | RCT, SB | Mixed (%FEP NR); stable; SZ + SZA | 64 MFG-adherence vs. 53 MFG-standard vs. 57 TAU | 12 m (FU at 18 m and 24 m) | Treatment Compliance Interview | Group effect (F = 6.41, p = 0.003); Time effect (F = 3.5, p = 0.009); Group × time effect n.s. | Group differences in time to first hospitalization (χ2 = 13.3, p = 0.001); at FU MFG-A vs. MFG-S (χ2 = 6.3, p = 0.01) and MFG-A vs. TAU (χ2 = 8.7, p = 0.003); hospitalization rate: MFG-A (39%) vs. MFG-S (66%) (χ2 = 8.2, p = 0.004), MFG-A vs TAU (70.2%) (χ2 = 11.3, p < 0.001); MFG-S vs. TAU (χ2 = 0.2, n.s.) | Low |
| Valencia et al. (2010) | RCT, SB | Mixed (%FEP NR); stable; SZ | 47 intervention vs. 36 TAU | 12 m | Prescription renewals, patient's and key relative's monthly report to the treating psychiatrist | Medication adherence 91.5 vs. 77.8% (p < 0.050); visit adherence 82.5 vs. 70% (p < 0.050) | Global functioning ES = 1.30 vs. TAU ES 0.30 (effect for time, group and time × group all p < 0.010); relapse rate 12.8 vs. 33.3%, p < 0.05; rehospitalization 2.1 vs. 14%, p < 0.050 | Low | |
| LAI | Noordraven et al. (2017) | Open label RCT | Chronic; stable; PSD | 84 intervention vs. 85 TAU | 12 m (+6 m FU) | MPR, longest uninterrupted period during which depot medication was received, time to first discontinuation of depot medication, total number of days without depot medication, and time between prescription date and the date the depot was actually received | MPR 14.9% (95% CI 8.9–20.9), p < 0.0001; good adherence (MPR ≥80 %) = 33.1% (95% CI 20.2–45.4), p = 0.031; 6 m FU MPR 6.5% (95% CI 2.0–10.9), p = 0.047; 6 m FU good adherence: 22.1% (95% CI 4.2–39.8%), p = 0.010 | Attitudes, clinical symptoms, psychosocial functioning, substance use, QoL, side effects (all n.s.) | Moderate |
| Lee et al. (2010) | CT—prospective, controlled, unrandomized | Mixed (% FEP NR); stable; SZ + SZA | 21 intervention vs. 25 TAU | 12 m (+FU at 2 y) | Visits for injection/planned visits for injection; treatment discontinuation; injection discontinuation | 1 y FU intervention: 94.6%, TAU: 75.9%, (t = 3.5, p < 0.010); 2 y FU intervention: 92.1%, TAU: 74.2%, (t = 2.7, p < 0.010); treatment discontinuation: intervention 14% vs. TAU 28% (χ2 = 6.0, p = 0.010); injection discontinuation: intervention 23% vs. TAU 68% (χ2 = 13.0, p < 0.010) | 1 y relapse rate intervention vs. TAU p < 0.010; 2 y relapse rate intervention vs. TAU χ2 = 4.2, p = 0.040; symptom severity n.s.; side effects n.s | Moderate | |
| Sajatovic et al. (2013) | CT—prospective, uncontrolled trial | Mixed (% FEP NR); state NR; SZ + SZA | 30 | 6 m | TRQ, MAQ, injection frequency | TRQ (incl. oral medication, mean) −38.9 (95% CI, −75.7–−2.0), p = 0.028; MAQ, mean (SD): 1.4 (1.6), p = 0.001; injection frequency, mean (SD): only at week 13: 83 (35), and week 25: 76 (35) | Improvements in psychiatric symptoms (p < 0.001; BPRS (t = 2.51, p = 0.029), PANSS (p = 0.005), CGI (p < 0.001), and functioning (p < 0.001), akathisia (40%); BMI and total cholesterol n.s.; changes in hospitalizations n.s. | Low | |
| Technology | Frangou et al. (2005) | RCT, open | Chronic; stable; SZ | 36 pill counting vs. 36 @HOME vs. 36 TAU | 8 w | MAQ-based questionnaire; pill counting; e-monitoring (incl. electronic dispenser) | TAU, mean (SD; range)%: 77.3 (22.1; 18–95)%; pill counting, mean (SD; range)% = 78.5% (14; 50–95); e-monitoring, mean (SD; range)%: mean of 92.3% (4.8; 82–100); effect of group (F = 8.9, p = 0.0001); TAU vs. pill counting (n.s.); e-monitoring group vs. TAU (p = 0.001); e-monitoring vs. pill counting group (p = 0.007) | Group differences in the PANSS total score (F = 5.7, p = 0.004); control vs. pill-counting group (p = 0.008) and e-monitoring (p = 0.04); pill-counting vs. e-monitoring (p = 0.8); end-point medical (p = 0.01) and emergency (p = 0.0001) visits in the @HOME patient, group difference (F = 3.6, p = 0.002) | Moderate |
| Montes et al. (2012) | RCT; open | Chronic; stable; SZ | 100 intervention vs. 154 TAU | 6 m (3 and 6 m) | MAQ | MAQ [mean (95% CI)] 3 m: mean total score change intervention-−1.0 (−1.02–−0.98) vs. TAU −0.7 (−0.72–−0.68) p = 0.02; 6 m: mean total score change intervention-−1.1 (−1.12–−1.08) vs. TAU 0.8 (0.81, 0.78), p = 0.04 | Symptom improvement [mean (95% CI)] 3 m: improvement in negative [intervention 3.3 (3.10–3.50) vs. TAU 3.5 (3.36–3.64), p = 0.020], cognitive [intervention 3.3 (3.12–3.48) vs. TAU 3.6 (3.46–3.74), p = 0.010] and global [intervention 3.2 (3.02–3.38) vs. TAU 3.5 (3.36–3.64), p = 0.012) symptoms; 6 m negative (n.s.), cognitive (n.s.) and global (n.s.) symptoms; attitude [mean (95% CI)] 3 m: intervention 2.0 (1.94, 2.06), vs. TAU 0.4 (0.35, 0.45), p = 0.0003; 6 m: intervention 2.3 (2.24, 2.36), vs. TAU 0.9 (0.85, 0.95), p = 0.002; insight n.s.; QoL intervention 6.6 (6.38–6.82) vs. TAU 3.1 (2.91–3.29), p < 0.03; 6 m: n.s. | Moderate | |
| Velligan et al. (2013) | RCT, SB | Chronic; stable; SZ + SZA | 46 MeM vs. 46 PharmCAT vs. 45 TAU | 9 m | Electronic monitor, pill counts | e-monitoring: treatment group effect F = 47.29, p < 0.0001; effects for time F = 0.06, n.s.; time × group effect F = 0.44, n.s.; PharmCAT vs. TAU ES = 1.03 and MeM vs. TAU ES = 0.98. Pill counts: significant main effect of group F = 7.83, p < 0.0001 and n.s. effects of time F = <1, n.s.; time × group interaction F = 2.34, p = 0.06; adherence rate PharmCAT 91% vs. MeM 86%, t = 2.05, p = 0.04; PHARMCAT 91% vs. TAU 80%, t = 3.95, p = 0.0001; MeM 86% vs. TAU 80%, t = 1.82, n.s. | All n.s. (p > 0.090; symptom severity and functioning) | Low | |
| Moncrieff et al. (2016) | RCT, open | Mixed (% FEP NR); state NR; PSD | 31 intervention vs. 29 TAU | 3m (FU 2–3 w; 2–3 m) | MAQ | OR = −0.44, 95% CI, −0.76–−0.11 | Positive attitudes to antipsychotic medication (DAI, 1.65; 95% CI, −0.09–3.40); PANSS, side effects and dosage (all n.s.) | Moderate | |
| Beebe et al. (2017) | RCT, SB | Mixed (% FEP NR); stable; SZ + SZA | 53 intervention vs. 52 TAU | 6 m | Pill counts; serum medication levels | Pill counts adherence: 66% vs. 50%, (χ2, n.s.); serum AP levels within therapeutic range: 54.7% vs. 32.7% (χ2 = 5.2, p = 0.023) | Low |