NIMH Director Thomas Insel Acknowledges That Antipsychotics May Worsen Long-Term Outcomes

NIMH Director Thomas Insel Acknowledges That Antipsychotics May Worsen Long-Term Outcomes | Mad In America

August 29, 2013

Thomas Insel, the director of the National Institute of Mental Health (NIMH), acknowledged yesterday in his “Director’s Blog” that the long-term outcome studies of Lex Wunderink and Martin Harrow indicate that antipsychotics, despite their apparent short-term benefits, “may worsen prospects for recovery” over the long-term. ”It appears that what we currently call “schizophrenia” may comprise disorders with quite different trajectories,” says Insel, “For some people, remaining on medication long-term might impede a full return to wellness. For others, discontinuing medication can be disastrous. For all, we need to realize that reducing the so-called ‘positive symptoms’ (hallucinations and delusions) may be necessary, but is rarely sufficient for a return to normal functioning.”antipsychotic medication, which seemed so important in the early phase of psychosis, appeared to worsen prospects for recovery over the long-term.

NIMH · Antipsychotics: Taking the Long View

By Thomas Insel on August 28, 2013

One of the first lessons I received as a psychiatrist-in-training 35 years ago was the value of antipsychotic medications. These medicines have been available for the treatment of psychosis for over half a century, beginning with the prototype first generation drug chlorpromazine (Thorazine) and now extending to some 20 different compounds, including several second-generation medications, often called “atypical antipsychotics.” Symptoms such as hallucinations, delusions, and paranoia are reduced reliably by these drugs. Although these symptoms can be frightening and dangerous for patients, family members, and providers, antipsychotics safely and effectively help people through the crisis of acute psychosis.

However, the long-term management of chronic mental illness is another matter. Recently, results from several studies have suggested that these medications may be less effective for the outcomes that matter most to people with serious mental illness: a full return to well-being and a productive place in society.

That is not to say that people are not remitting or recovering from serious mental illness. An article recently posted online in JAMA-Psychiatry tells an interesting story about medications and recovery.1 Wunderink and colleagues from the Netherlands report on a seven-year follow-up of 103 people with schizophrenia and related disorders who had experienced a first episode of psychosis between 2001 and 2002. After six months of symptomatic remission following antipsychotic treatment, patients were randomly assigned to either maintenance antipsychotic treatment or a tapering-off and discontinuation of the drug. As expected, the group that stopped taking their medications experienced twice the relapse rates in the early phase of the follow-up. But these rates evened out after a few years, as some patients in the maintenance group also stopped taking their medication. Most important, by seven years, the discontinuation group had achieved twice the functional recovery rate: 40.4 percent vs. only 17.6 percent among the medication maintenance group. To be clear, this study started with patients in remission and only 17 of the 103 patients—21 percent of the discontinuation group and 11 percent of the maintenance group—were off medication entirely during the last two years of follow-up. An equal number were taking very low doses of medication—meaning that roughly one-third of all study patients were eventually taking little or no medication.

For me, there were three remarkable results in this study. First, the groups did not ultimately differ in their experience of symptoms: about two-thirds of each group reported significant improvement in symptoms at seven years. Second, 29 percent of the discontinuation group reported that they had also achieved a healthy outcome in work and family life—a number that should give hope to those struggling with serious mental illness. And finally, antipsychotic medication, which seemed so important in the early phase of psychosis, appeared to worsen prospects for recovery over the long-term. Or, as Patrick McGorry said in an accompanying editorial, “less is more.”2 At least for these patients, tapering off medication early seemed to be associated with better long-term outcomes.

What does this say about the long-term use of antipsychotics? Are they potentially harmful? Are they necessary for an individual’s entire lifetime? Earlier this year, Martin Harrow and Thomas Jobe reported an analysis of several long-term follow-up studies of people with schizophrenia to determine if antipsychotics, given long-term, facilitate a return to functional well-being.3 They describe the following pattern across these studies: (a) within the first 6-10 months after discontinuation, 25-55 percent of patients relapse; (b) for those who do not relapse during this period, subsequent relapses are much less frequent even after prolonged periods off medication.

It appears that what we currently call “schizophrenia” may comprise disorders with quite different trajectories. For some people, remaining on medication long-term might impede a full return to wellness. For others, discontinuing medication can be disastrous. For all, we need to realize that reducing the so-called “positive symptoms” (hallucinations and delusions) may be necessary, but is rarely sufficient for a return to normal functioning. Neither first nor second generation antipsychotic medications do much to help with the so-called negative symptoms (lack of feeling, lack of motivation) or the problems with attention and judgment that may be major barriers to leading a productive, healthy life. Family education, supported employment, and cognitive behavioral therapy have all demonstrated efficacy in reducing the likelihood of relapse events, increasing the ability to function in daily life, and improving problem-solving and interpersonal skills.

NIMH is supporting research on interventions that focus on a combination of approaches—symptom remission, family engagement, and functional recovery. The Recovery After Initial Schizophrenia Episode (RAISE) project combines low-dose medication with family psycho-education, supported education/employment, individual resilience training, and other interventions to focus on more than just the psychotic symptoms.4Combining current treatments, as done in RAISE, looks like a promising approach.5,6,7

We realize that for too many people, today’s treatments are not good enough. New, better treatments are essential if we are to improve outcomes for all – that is the promise of research. But in the meantime, we need to be thoughtful about the treatments we have. Clearly, some individuals need to be on medication continually to avoid relapse. At the same time, we need to ask whether in the long-term, some individuals with a history of psychosis may do better off medication. This is a tough call, where known risks need to be balanced against potential benefits. As the RAISE project has emphasized, shared decision-making between patients, families, and providers is essential for long-term management of psychotic disorders.

These new data on the long-term outcomes for people with “schizophrenia” remind us that 100 years after defining this disorder and 50 years after “breakthrough” medications, we still have much to learn.
References

1 Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. 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. JAMA Psychiatry. 2013 Jul 3. [Epub ahead of print] PMID: 23824214

2 McGorry P, Alvarez-Jimenez M, Killackey E. Antipsychotic Medication During the Critical Period Following Remission From First-Episode Psychosis: Less Is More. JAMA Psychiatry. 2013 Jul 3. [Epub ahead of print] PMID: 23824206

3 Harrow M, Jobe TH. Does Long-Term Treatment of Schizophrenia With Antipsychotic Medications Facilitate Recovery? Schizophr Bull. 2013 Mar 19. [Epub ahead of print] PMID: 23512950

4 Early Detection and Intervention in Schizophrenia: A new Therapeutic Model. Lieberman JA, Dixon LB, Goldman HH. JAMA. 2013;310(7):689-690.

5 Craig TK, Garety P, Power P, Rahaman N, Colbert S, Fornells-Ambrojo M, Dunn G. The Lambeth Early Onset (LEO) Team: randomised controlled trial of the effectiveness of specialised care for early psychosis. BMJ. 2004 Nov 6;329(7474):1067. PMID: 15485934

6 Grawe RW, Falloon IR, Widen JH, Skogvoll E. Two years of continued early treatment for recent-onset schizophrenia: a randomised controlled study. Acta Psychiatr Scand. 2006 Nov;114(5):328-36. PMID: 17022792

7 Petersen L, Jeppesen P, Thorup A, Abel MB, Øhlenschlaeger J, Christensen TØ, Krarup G, Jørgensen P, Nordentoft M. A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ. 2005 Sep 17;331(7517):602. PMID: 16141449

[newtus]

i know he would say that. and i agree.

[Sometimes psychotic]

Thanks so much for this, I hadn't heard!

Addiction Today: 5,000 WOMEN POISONED EACH YEAR

In the continuum of care, of course harm reduction has its place – when that phrase defines actions which truly reduce harm. Sadly, however, it is too often used to mask actions which aggravate harm: overprescribing of drugs is one such instance which ignores what should be the core of all medical care: “First do no harm”. That there were 5,012 episodes of women being admitted to hospitals in England last year for poisoning (*and side effects/withdrawal problems) by benzodiazepines, and 3,379 for other ‘Z drugs’, shows that adage was ignored by too many prescribers. It is also shown by another 8,501 admissions for women poisoned by “unspecified antidepressants” or SSRIs, on top of 2,392 by “tricyclic and tetracyclic antidepressants”.
Poisoning by salicylates, commonly found in aspirin, led to 1,289 women in hospital.
These statistics are for last year alone. The past six years add up to 104,210 admissions for women poisoned by benzodiazepines alone. What is the cost not only to the NHS but also to the children who depend on these women? What is the cost to the rest of their families and society?
The cold facts also indicate perhaps more than anything that the so-called war on drugs is being won, as there were only 19 hospital admissions for women poisoned by opium, 243 by heroin, 186 by cocaine, 31 by cannabis and 13 by LSD. The figures soar for drugs which might escape this net: there were 4,355 hospital admissions for women poisoned by “other opioids”.
Poisonings by methadone totalled only 240, although it is second only to benzodiazepines for drug-related deaths in England.
POISONINGS OF MEN AND CHILDREN
A freedom-of-information question has been posed by Mick Behan to get the equivalent drug-poisoning statistics for men and for children – but has been refused by the Department of Health.
WHY DID IT TAKE SO LONG TO GET THE FACTS?
Over 20 years ago, I witnessed the harms from benzos: rehab patients who had used them could not recover as quickly as even ‘hardcore’ heroin addicts. Campaigners such as Behan and Barry Haslam have been seeking help on this issue for over three decades. “There are no appropriate services even when people get to hospital Accident & Emergency,” Behan said. “There is no treatment plan so they are sent back to their GP or psychiatrist... who give more prescriptions.”
Theories abound as to why overprescribing is a public-health problem, from pharmaceutical companies chasing profit to undertrained healthcare professionals feeling the need to “do something” especially when led unwittingly by pharmaceutical opinion-leaders, to doctors being paid to prescribe rather than get people off drugs, to the black market in prescribed drugs, and more.
The 2011 National Treatment Agency and National Addiction Centre reports on Addiction to prescribed medicines did not help. First, a misleading statistic in the NTA report implied that the scale of the problem was only 3,735 people (not also on opiates) – the reality was 1.5million prescribed-benzodiazepine addicts, as estimated by Professor Heather Ashton in 2001, missed by the NTA ‘treatment’ regime.
Second, the reports stated that patients have no difficulty finding local help. In reality, there is little help available and the few charity helplines are inundated. GPs have nowhere to obtain expert help for their patients. Read more anomalies here.
A telling survey about lack of help came in June 2012 with the Survey of Primary Care Trusts in England recording provision of services for involuntary tranquilliser addiction by John Perrott, under the aegis of the All-Party Parliamentary Group for Involuntary Tranquilliser Addiction chaired by Jim Dobbin MP. Out of 149 primary care trusts questioned, only six said they could care for long-term benzodiazepine users/dependents.
MORE INFORMATION
Useful reference and campaign libraries can be found at www.appgita.com and www.benzo.org.uk.