It’s something of an understatement to say that schizophrenia spectrum disorders (SSD) can be tough to live with. But it certainly helps explain the unsettling data a group of Canadian researchers unearthed: One in 58 people committed suicide within four years of an SSD diagnosis.
Consequently, relapse prevention persists as a daunting challenge in schizophrenia treatment, especially for patients who’ve already faced their first psychotic episode.
Now, a new population-based study out of Finland appearing in The Lancet Psychiatry, offers fresh insight into how different antipsychotic treatment strategies can influence relapse risks after a first episode of schizophrenia. What the researchers found could upend existing treatment guidelines and cut a new path to better outcomes.
Tackling the Schizophrenia Knowledge Gap
Effective schizophrenia treatment typically demands an extended antipsychotic regime to maintain remission and keep relapses at bay. It’s a never ending battle.
While most patients usually respond well to early treatment efforts, relapses can hamper efficacy as time wears on. Established treatment guidelines advise clozapine as a third-line treatment. And that’s only after patients fail to respond to at least two other antipsychotics.
But it’s not unusual for patients to put off taking the antipsychotic over widespread concerns about side effects.
Established research reveals a treatment prejudice that favors response or remission, which leaves sizable gaps in understanding how to prevent those relapses in the first place. And it leaves some questions unanswered, such as whether switching antipsychotics or introducing clozapine earlier could make a difference.
Study Design and Methods
One international group of researchers sought to change that. To do so, they worked off of Finland’s national healthcare registry to analyze data from 3,000 patients 45 or younger who’d received a diagnosis of first-episode schizophrenia and experienced an initial psychosis relapse between 1996 and 2014. The team also considered patients who’d relapsed within five years of their initial hospital discharge.
The team broke the treatment strategies used 30 days before and after the first relapse into one of five groups:
- Non-clozapine oral antipsychotic monotherapy.
- Non-clozapine oral antipsychotic polypharmacy.
- Clozapine.
- Long-acting injectable antipsychotics.
- No antipsychotic use.
Using statistical models, researchers calculated adjusted hazard ratios (aHR) to measure the risk of a second relapse within two years, based on the treatment type.
The results were startling. Nearly 72 percent of patients experienced a second relapse within two years.
Switching to Clozapine Showed Benefits…
Switching to clozapine reduced the risk of a second relapse among those who’d experienced their first relapse while on non-clozapine oral antipsychotics. The adjusted hazard ratio (aHR) for relapse was 0.66, a 34 percent reduction compared to maintaining the status quo.
Patients who switched from antipsychotic non-use to clozapine benefited even more, boasting an aHR of 0.52.
Similarly, those switching from polypharmacy to clozapine enjoyed a dramatic reduction in relapse risk with an aHR 0.30.
…But Other Approaches Fell Short
On the flip side, switching from one non-clozapine oral antipsychotic to another offered no reduction in relapse risk. Continuing the same treatment after relapse or stopping antipsychotics altogether also failed to make a difference.
Patients already on clozapine before their first relapse benefited the most from staying on clozapine. But making the move from clozapine to other treatments exposed an elevated relapse risk.
Regrettably, nearly half of the patients – 45.5 percent – hadn’t been on any antipsychotics before their first relapse, confirming suspected gaps in treatment adherence (or access). After relapsing, many patients avoided treatment altogether, making them vulnerable to further relapses.
Implications for Schizophrenia
The results of this study flies in the face of legacy protocols that delay clozapine use until third-line treatment. Because of that, the authors insist that caregivers should consider clozapine earlier in the treatment sequence, particularly after a first relapse.
The evidence, they claim, also reinforces clozapine’s superior efficacy for preventing relapses, even in non-treatment-resistant schizophrenia. Shared decision-making between clinicians, patients, and caregivers should consider clozapine’s benefits and risks.
Broader Context
The findings build on earlier research showing that antipsychotic effectiveness tapers off after multiple relapses, which makes early intervention that much more important. With clozapine repeatedly emerging as the most effective option, the authors argue for changes in prescription practices to prevent any delays in clozapine adoption.
Relapse prevention remains critical for improving schizophrenia outcomes. This study offers some of the most compelling evidence to date that switching to clozapine after an initial relapse dramatically reduces the risk of subsequent relapses. And as more patients benefit from timely and effective treatment strategies, this research marks a crucial step forward in transforming care for schizophrenia patients.
“It is also crucial that implementation science be at the forefront of efforts to increase the effectiveness, adoption, and scalability of treatments, with an emphasis on tailoring for target contexts and bolstering existing services with provider-level and organisational-level training, flexibility, and resources,” the University of Michigan’s Lindsay Bornheimer concluded in a separate comment in the same issue of the Lancet.
Further Reading
The Road Between The Gut And Schizophrenia Runs Both Ways
Unified Brain Network Links Schizophrenia Atrophy
Gut Microbiome Breakthroughs Revolutionize Schizophrenia Treatment
