Wunderink, 2013 Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy...

[Altostrata]

After 7 years, patients reduced or discontinued antipsychotic drugs had twice the recovery rate of the patients maintained on drugs.

 

JAMA Psychiatry. 2013 Sep;70(9):913-20. doi: 10.1001/jamapsychiatry.2013.19.

Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial.
Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ.

Abstract at http://www.ncbi.nlm.nih.gov/pubmed/23824214

IMPORTANCE:
Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before.

OBJECTIVE:
To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial.

DESIGN:
Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR.

SETTING:
One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment.

INTERVENTION:
After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician.

MAIN OUTCOMES AND MEASURES:
Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters.

RESULTS:
The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates.

CONCLUSIONS AND RELEVANCE:
Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice.

[Altostrata]

Discussion from http://www.medscape.com/viewarticle/807894

Antipsychotics in First-Episode Psychosis: Less Is More
Nancy A. Melville July 16, 2013

 

Patients treated with antipsychotics after remission of a first episode of psychosis are substantially more likely to experience long-term recovery if treated with a dose-reduction or discontinuation strategy vs maintenance therapy, a long-term follow-up study shows.

 

Shorter-term outcome studies have consistently shown higher relapse rates with the dose-reduction/discontinuation approach, but the study is said to be among the first to provide a longer-term perspective on the issue, with a follow-up period as long as 7 years.

 

"To our knowledge, this is the first study showing long-term gains of an early-course dose-reduction strategy in patients with remitted first-episode psychosis," the authors write.

....
Functional Remission
Investigators led by Lex Wunderink, MD, PhD, of Friesland Mental Health Services, in Leeuwarden, the Netherlands, conducted a 7-year follow-up of 103 patients who had originally been part of a 2-year randomized clinical trial comparing maintenance therapy with dose-reduction/discontinuation treatment.

 

In the original study, 257 patients with first-episode psychosis presenting between October 2001 and December 2002 were asked to participate in the trial. Among them, 111 refused or were lost to follow-up, and 18 did not experience remission.

 

The remaining 128 were randomly assigned to receive either maintenance therapy or dose-reduction/discontinuation therapy for 18 months, starting after 6 months of remission from their first episode of psychosis.

 

At the conclusion of that study, relapse rates, consistent with previous research, were significantly higher in the dose-reduction/discontinuation group, compared with those on maintenance therapy, and there were no improvements with dose reduction in functional remission.

 

The follow-up at 7 years of 103 patients from the original study, however, showed the rate of recovery, defined according to criteria for symptomatic and functional remission for at least 6 months at the 7-year follow-up, in the dose-reduction/discontinuation group (40.4%) to be more than twice the rate in the maintenance therapy group (17.6%).

 

Functional remission in the dose-reduction/discontinuation group was 46.2% vs 19.6% in the maintenance group; however, there were no differences between the 2 groups in terms of symptomatic remission.

 

According to Dr. Wunderink, the distinction between functional and symptomatic remission is important.

"The functional domain is what matters most from a patient perspective," he told Medscape Medical News.

"These gains were not apparent after 2 years of follow-up, just after applying the strategy for 18 months, but only after longer-term follow-up, in our case, after 7 years. Gains might already have shown up after 3 or 4 years, but we don't exactly know," he noted.

At 7-year follow-up, "relapse rates came on par and functional recovery was far better in patients who were discontinued in the original trial," he said.

 

Although the study did not specify which antipsychotics drugs were used, owing to low numbers, Dr. Wunderink said that they included the most common antipsychotics, including risperidone, olanzapine, and clozapine, with lower percentages of aripiprazole, quetiapine, and first-generation antipsychotics.

 

Probable Mechanism
The authors hypothesized that the long-term improvements associated with dose reduction or discontinuation are directly associated with the role of dopaminergic blockage in psychosis treatment possibly diminishing over time.

 

"The underlying background [of the study] was our hypothesis that dopaminergic blockade is a good and necessary means of symptomatic treatment of positive symptoms of the acute episode but does not really touch underlying pathological mechanisms of most psychoses, including schizophrenia's, that are still unknown to a large extent," Dr. Wunderink explained.

 

"We felt that dopaminergic blockade might have a negative impact on functional capacity, which in the end turned out to be true — endorsed by the long-term results — unexpectedly.

 

Over time, the lower antipsychotic load in the dose-reduction group "took away the redundant dopamine blockage, and that allowed for better functional recovery," he said.
....
"[The findings] mean that we do have to consider dose-reduction strategies in all first-episode patients who are free of symptoms and meet the remission criteria, in order to promote functional recovery," he said.

 

"These dose-reduction strategies should be further elaborated, for instance, by adding psychological interventions like cognitive-behavior therapy and individual placement and support to pharmacological treatment."

 

Need for Replication
In an accompanying editorial, Patrick McGorry, MD, PhD, of the University of Melbourne, in Victoria, Australia, and colleagues agreed that the therapeutic strategies should be implemented whenever possible, and they called for clinicians to more carefully consider which patients may be appropriate for antipsychotic dose reduction.

 

"It now seems probable for patients who achieve clinical remission from first-episode psychosis that as many as 40% can achieve a good long-term recovery with use of no or low-dose antipsychotic medication," they write.

 

"It is important to identify these patients at an early stage."

 

In further commenting on the study to Medscape Medical News, Dr. McGorry called the research "groundbreaking," but he noted that the findings will need to be replicated in order to have serious influence.

 

He added that although many clinicians are inclined to err on the side of caution by keeping patients on maintenance therapy, the findings suggest that even an approach of trying a lower dose, as opposed to discontinuation, may offer improved recovery in the long run.

 

"This will be a challenge to many clinicians; however, dose reduction is a more cautious goal than discontinuation, and all clinicians should embrace that, at least in patients with good early remissions," Dr. McGorry said.

 

"More intensive psychosocial care aimed at functional recovery could further enhance recovery rates if offered via specialized early-psychosis services," he said.

 

Valuable Insights
Dr. Philip R. Muskin, MD, a professor of psychiatry at the Columbia University Medical Center in New York City, agreed that the study has important limitations, particularly in that the patients appear to have relatively mild psychosis, but the research nevertheless offers valuable insights, he said.

 

"This has got to be one of the longest studies that have ever been done, and they have pretty convincing data that people do better with dose reduction," he told Medscape Medical News.

 

"And I like their argument that function matters more than symptoms," he said, noting reports of patients who experience psychotic symptoms but who are able to function well in society, even in positions such as CEOs.

 

"I think what you can take from this study is that if you treat a patient for a year — particularly someone with mild symptoms and who responds to a relatively low dose of medication — you can probably consider not maintaining them forever, and perhaps try a trial of slow dosage reduction and careful follow-up," he said.

 

"You may find the patient winds up doing better and no longer needs the medication."

 

"It doesn't necessarily have to be all or nothing," he added. "It looks like the big risk period is the first few years, but as long as they do okay, those first few years they should be okay."
....

[Altostrata]

I don't have the full text; I'd like to know their discontinuation protocol.

 

Joanna Moncrieff refers to it here http://joannamoncrieff.com/2013/12/20/psychiatry-has-its-heads-in-the-sand-royal-college-of-psychiatrist-rejects-discussion-of-crucial-research-on-antipsychotics/
 

This study, conducted with people who had recovered from a first episode of psychosis, found that people randomised to a flexible and gradual antipsychotic discontinuation strategy were twice as likely to show a full social recovery than those who were allocated to continuous (maintenance) antipsychotic treatment. Moreover, relapses, which had been higher in the discontinuation group at 18 month follow up, had equalised.

 

[Abilifyneedhelp88]

After 7 years, patients reduced or discontinued antipsychotic drugs had twice the recovery rate of the patients maintained on drugs.

 

JAMA Psychiatry. 2013 Sep;70(9):913-20. doi: 10.1001/jamapsychiatry.2013.19.

 

Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial.

Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ.

 

Abstract at http://www.ncbi.nlm.nih.gov/pubmed/23824214

 

IMPORTANCE:

Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before.

 

OBJECTIVE:

To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial.

 

DESIGN:

Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR.

 

SETTING:

One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment.

 

INTERVENTION:

After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician.

 

MAIN OUTCOMES AND MEASURES:

Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters.

 

RESULTS:

The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates.

 

CONCLUSIONS AND RELEVANCE:

Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice.

All I can say is that this is proof that people do not need these drugs.....It is the coming on and coming off that makes people sick...The doctors are criminal in nature for ever suggesting and lying to patients that they had a disorder and we are just as guilty to believe them....They are wrong and should be force fed these medications themselves....to see for themselves the harm they are doing to people....I hate any psychiatrist that thinks they are helping people by prescribing these drugs....They are pathetic and wish I never listened or got myself entangled with them whatsoever....We should not be so entrusting of doctors for they are fallible and look out for themselves and many times have no interest in serving the patient but to fill their own pocketbook...The Hippocratic oath contends to do no harm....They have screwed up more people for having natural moods and sometimes depression. I have to agree with Stevie Nicks who said the worst decision she ever made was to go to a psychiatrist. I have to agree...They are all evil....and not to be listened to...