Short-term exposure to antipsychotics has proven to be beneficial. However, naturalistic studies are lacking regarding the long-term use of antipsychotics. This study aimed to investigate changes in use of antipsychotics over 20 years after a first-episode schizophrenia.

This study is part of the Danish OPUS trial (1998–2000), including 496 participants with first-episode schizophrenia. Participants were reassessed four times over 20 years. The main outcomes were days on medication, redeemed prescriptions of clozapine, psychiatric hospitalizations, and employment.

At the 20-year follow-up, an attrition of 71% was detected. In total, 143 out of 496 participated, with 36% (n = 51) in remission-of-psychotic-symptoms-off-medication. The lowest number of days on medication (mean [s.d.], 339 [538] days) was observed in this group over 20 years. Register data on redeemed antipsychotics were available for all trial participants (n = 416). Individuals in treatment with antipsychotics (n = 120) at the 20-year follow-up had spent significantly more days in treatment (5405 [1857] v. 1434 [1819] mean days, p = 0.00) and more had ever redeemed a prescription of clozapine (25% v. 7.8%, p = 0.00) than individuals who had discontinued antipsychotics (n = 296). Further, discontinuers had significantly higher employment at the 20-year follow-up (28.4% v. 12.5%, p = 0.00).

In a cohort of individuals with first-episode schizophrenia, 36% were in remission-of-psychotic-symptoms-off-medication. However, high attrition was detected, potentially affecting study results by inflating results from individuals with favorable outcomes. From register data, free from attrition, approximately 30% were in treatment with antipsychotics, and 70% had discontinued antipsychotics. Individuals in treatment had the least favorable outcomes, implying greater illness severity.

Studies investigating parenthood and how it affects long-term outcomes are lacking among individuals with schizophrenia spectrum disorders. This study aimed to examine the life of participants 20 years after their first diagnosis with a special focus on parenthood, clinical illness course, and family-related outcomes.

Among 578 individuals diagnosed with first-episode schizophrenia spectrum disorder between 1998 and 2000, a sample of 174 participants was reassessed at the 20-year follow-up. We compared symptom severity, remission, clinical recovery, and global functioning between 75 parents and 99 non-parents. Also, family functioning scored on the family assessment device, and the children's mental health was reported. We collected longitudinal data on psychiatric admission, supported housing, and work status via the Danish registers.

Participants with offspring had significantly lower psychotic (mean (s.d.) of 0.89 (1.46) v. 1.37 (1.44), p = 0.031) negative (mean [s.d.] of 1.13 [1.16] v. 1.91 [1.07], p < 0.001) and disorganized symptom scores (mean [s.d.] of 0.46 [0.80] v. 0.85 [0.95], p = 0.005) and more were in remission (59.5% v. 22.4%, p < 0.001) and in clinical recovery (29.7% v. 11.1%, p = 0.002) compared to non-parents. When investigating global functioning over 20 years, individuals becoming parents after their first diagnosis scored higher than individuals becoming parents before their first diagnosis and non-parents. Regarding family-related outcomes, 28.6% reported unhealthy family functioning, and 10% of the children experienced daily life difficulties.

Overall, parents have more favorable long-term outcomes than non-parents. Still, parents experience possible challenges regarding family functioning, and a minority of their children face difficulties in daily life.

Cognitive deficits are a core feature of schizophrenia and are closely associated with poor functional outcomes. It remains unclear if cognitive deficits progress over time or remain stable. Determining patients at increased risk of progressive worsening might help targeted neurocognitive remediation approaches.

This 20-year follow-up study examined neurocognitive outcomes of 156 participants from the OPUS I trial. Neurocognition was assessed using the brief assessment of cognition in schizophrenia at the 10- and 20-year follow-up, allowing us to examine changes in neurocognition over ten years.

We found that 30.5% of patients had a declining course of neurocognition, 49.2% had a stable course of neurocognition and 20.3% experienced improvements in neurocognition. Good cognitive functioning at the 20-year follow-up was significantly associated with higher levels of social functioning (B 6.86, CI 4.71–9.02, p < 0.001) while increasing experiential negative symptoms were significantly correlated to cognitive worsening (PC-0.231, p = 0.029). Younger age at inclusion (B: 0.23 per 10-years, CI 0.00–0.045, p = 0.047) and low level of education (below ten years) (mean difference: −0.346, CI −0.616 to −0.076, p = 0.012) predicted declining neurocognition.

Our findings support the notion of different schizophrenia subtypes with varying trajectories. Neurocognitive impairment at the 20-year follow-up was associated with other poor outcomes, highlighting the importance of treatments aimed at improving neurocognition in patients with schizophrenia spectrum disorders.

Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death.

Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995–2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2–5. Outcomes year 5–6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression.

Among 21 351, 9.3% took antipsychotics continuously year 2–5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53–2.56 and OR 2.60, 95% CI 1.91–3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05–1.48 and 2.04, 95% CI 1.64–2.53) and no antipsychotics (OR 2.00, 95% CI 1.69–2.38 and 5.64, 95% CI 4.56–6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10–1.47) and longer admissions (IRR 1.68, 95% CI 1.30–2.16) year 5–6 compared to continuous users. Mortality during year 5–6 did not differ between groups.

Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.

The effect of antipsychotics medication on cognitive functioning in patients diagnosed with schizophrenia is poorly understood. Some studies of second generation antipsychotics indicated that they improved cognitive functioning while other studies have found that they decrease the level of cognitive functioning.

We included patients with schizophrenia who were in treatment with antipsychotics 1.5 years (baseline) after initiation of treatment and followed them up 3.5 years later (n = 189). At follow-up 60 (32%) had discontinued their antipsychotic treatment and 129 (68%) were still taking antipsychotics. Using the Brief Assessment of Cognition in Schizophrenia (BACS) we assessed cognition at baseline and follow-up.

The patients who discontinued their medication had a higher level of cognitive functioning in all domains at baseline, as well as Global cognitive function [mean z-score −1.50 (s.d. 1.24) v. −2.27 (s.d. 1.30), p = 0.00015]. After controlling for relevant confounders those who discontinued antipsychotic medication improved significantly more than those who remained on antipsychotic medication during the course of the follow-up on the Token Motor task [estimated mean change difference −0.46 (95% CI −0.89 to −0.04)], the Speed of Processing Domain [estimated mean change difference −0.38 (95% CI −0.68 to −0.08)] and global cognition [estimated mean change difference −0.36 (95% CI −0.66 to −0.07)].

Due to the naturalistic design, we cannot conclude on the direction of the relationship between antipsychotics and cognition. There is no evidence that discontinuation of medication had a negative effect on cognitive functioning. Rather, we found that that discontinuation of medication was associated with better cognitive functioning.