ADFD

The drugs do work: antidepressants are effective, study shows

Doctors hope study will put to rest doubts about the medicine, and help to address global under-treatment of depression

It’s official: antidepressants are not snake oil or a conspiracy

Findings

We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72–0·97) and fluoxetine (0·88, 0·80–0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01–1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses.

The Cipriani paper discussed today is junk. It is based on ghostwritten papers with no access to the data. No one - not MHRA or FDA have had access - none of the notional authors of these papers have had access - none can let an independent expert see what the data shows

Re Cipriani: In the case of at least one of these drugs - paroxetine - there have been fraud charges for overhyping the benefits and hiding the harms - we have to assume the same holds true for pretty well every paper that is part of this review

Re Cipriani et al: Lots of doctors in UK, Canada, etc use sertraline today based on a similar paper some yrs ago by Dr C which made sertraline out to be the best SSRI - but when the unpublished sertraline trials are taken into account it may be the worst

Re Cipriani et al: an earlier paper by this group looking at pediatric trials concluded Prozac works - when the FDA reviews of the trials for this drug in children show it is negative for the primary outcomes.

Re Cipriani et al: Dr Cipriani and SMC opinion leaders know the articles behind this are junk. This paper contributes to a misleading of doctors and patients. All concerned would be doing a more important and noble job if they were to tell doctors and patients this.

This statement is irresponsible and unsubstantiated, as the study actually supports what has been known for a long time, that various drugs can, unsurprisingly, have an impact on our mood, thoughts and motivation, but also differences between placebo and antidepressants are so minor that they are clinically insignificant, hardly registering at all in a person’s actual experience.

This study, and the media coverage that has accompanied it, will unfortunately do nothing to help reduce this level of unnecessary prescribing and the consequent harms.

More drugs are not the answer

“I agree that for some people antidepressant drugs are effective in raising mood or stimulating activity in the short term. This is not really very surprising, as we have known for about 20,000 years that various chemicals can be stimulating, can address tiredness or lethargy, can stimulate the reward systems of the brain and can raise mood. There are major industries – legal and illegal – built on that fact. So, I’m not hugely surprised that drugs can affect our mood.

“And there were some important issues in today’s research that we need to bear in mind. People who were known not to benefit from antidepressants weren’t included in this study. The research focussed on short-term benefits (8 weeks) in people with severe or moderate depression. Most people are not advised to limit their use of these drugs only to 8 weeks (most people take antidepressants for many months and years), and this study tells us nothing about their affects – including adverse effects – over the long or medium-term. The short-term effects may well be benefits, but we need to be mindful of long-term adverse effects. So, I’m sceptical of the claim that a million MORE people should be offered the drugs.

“We know drugs can raise our moods. That’s important. It may be something we want to contemplate when considering help, but it doesn’t really change a great deal. In particular, this research doesn’t speak of what the experience of depression actually is. Nor does it explore the disease model of mental health or offer insights into the causal processes that might lead people to be depressed. It’s important – at least in my opinion – to remember that, even when medication can help alleviate distress, that is not necessarily evidence that a biological disease process lies behind our mental health problems. We know that our mental health is intimately related to the things that happen to us, the circumstances of our lives, and how we make sense of this.

“In my opinion we should respect anything that helps people, but our real focus should be on understanding, and addressing, those factors in our lives that give rise to the hopelessness and low mood that so many people are suffering from. While many people find medication helpful, I’m not convinced that drugs should be seen as solutions to more systematic social and personal problems.”

Wer hat's bezahlt?

Die aktuelle Arbeit wurde nicht von Pharmaunternehmen finanziert. Aber knapp 80 Prozent der ausgewerteten Studien wurden im Auftrag von Medikamentenherstellern durchgeführt. Einige der an der Analyse beteiligten Forscher geben an, von verschiedenen Pharmakonzernen Vortrags- oder Beraterhonorare erhalten zu haben.

. Allerdings lässt sich trotz des Datenbergs einiges nicht beantworten. Beispielsweise gibt es keine Aufschlüsselung der Patienten nach Alter oder Geschlecht - und entsprechend auch keine daran angepassten Empfehlungen.

Die Arbeit kann auch nicht beantworten, welches Mittel möglicherweise Patienten mit einer therapieresistenten Depression, einer bipolaren Störung oder einer mit Wahnvorstellungen einhergehenden Depression besser hilft, denn das wurde in den Studien nicht untersucht. Weil nur Erwachsene an den Studien teilnahmen, lässt die Analyse auch keine Schlüsse über die Medikamentenwahl bei Kindern und Jugendlichen zu.

Und sie sagt nichts über den kombinierten Nutzen von Psychotherapie und Medikamenten oder zu anderen Therapiemöglichkeiten aus.

Wie es den Patienten nach einem halben Jahr oder einem Jahr ging, wissen wir ebenfalls nicht, da der gewählte Zeitraum acht Wochen waren. Deshalb ist zum Beispiel auch nicht erfasst, wie viele Patienten erst später unter Nebenwirkungen der Medikamente litten.

Dr James Davies, from the Council for Evidence-based Psychiatry, is distinctly unimpressed. He calls Dr Cipriani's claim to have the 'final answer' to be both 'irresponsible and unsubstantiated'.

Dr Davies says that while the new study shows antidepressant drugs to be better than placebo pills at lifting people's moods, 'the differences between placebo and antidepressants are so minor that they are clinically insignificant. They hardly register at all in a person's actual experience.'

The level of mood improvement being claimed does seem remarkably modest — not least when you realise that the nearly 80 per cent of the studies analysed by the Oxford study had been funded by pharmaceutical companies, which of course have a financial interest in the promotion of the drugs.

Much of what they analysed was unpublished research, too, which means it had not undergone the sort of rigorous peer-review required by medical journals that ensures the results are unaffected by poorly designed studies or outright financial bias.

Just as importantly, the drug trials studied by the Oxford analysis covered only eight weeks of antidepressant use, before it was judged whether the patients had benefited or not.

Around half of people prescribed antidepressants are on them for more than two years. 'This study tells us nothing about their effects over the long or medium term,' points out Dr Davies. 'In fact,' he adds, 'There is no evidence that long-term use has any benefits, and in real world trials the outcomes are very poor.'

The study period of eight weeks also completely ignores a problem that has dogged millions of long-term antidepressant patients over the decades: the sheer hell of getting off the drugs.

There are numerous patient groups on the internet dedicated to helping victims wean themselves off antidepressants, in the face of withdrawal effects that include plummeting mood levels and suicidal thoughts, a loss of libido and bizarre physical manifestations such as electric shock sensations.

Wissenschaftler haben in einer großen Analyse, die in der Fachzeitschrift „The Lancet“ veröffentlicht wurde, insgesamt 522 Studien aus den vergangenen Jahrzehnten zur Wirksamkeit von Antidepressiva ausgewertet.

Antidepressiva sind eine der meistverschriebenen Medikamentenklassen. Deswegen interessiert die Forschung dazu nicht nur die Wissenschaftler selbst, sondern auch die Öffentlichkeit. Umso wichtiger ist, dass diese Forschung gut gemacht ist. Es gibt erste Hinweise, dass die aktuell in vielen Medien behandelte Cipriani-Studie mit ihren Erfolgsmeldungen nicht gut gemacht wurde.

Beendet den Streit um die Psychopharmaka!

All das Unken der Pseudoaufklärer muss aufhören: Medikamente gegen die Depression sind keine Wunderpillen, aber sie helfen vielen Betroffenen zumindest etwas.

Kommentar von Christian Weber
Vielleicht muss es tatsächlich noch mal gesagt werden, also gut, ein letztes Mal: Ja, Antidepressiva wirken; nicht wahnsinnig gut, aber sie wirken, besser als Placebo und insbesondere bei schwereren Depressionen. Und sie sind einigermaßen verträglich.

Aber womöglich ist diese Botschaft noch nicht überall angekommen, denn immer noch finden sich zahlreiche Berichte in pseudoaufklärerischen Medien und erst recht im Netz, wonach Medikamente gegen Depressionen keinerlei Wirkung hätten. Immer noch kursieren Befürchtungen, dass Antidepressiva abhängig machen und die Persönlichkeit verändern, obwohl das frei erfundener Unfug ist.

Joanna Moncrieff hat geschrieben:Challenging the new hype about Antidepressants

The extraordinary media hype over the latest meta-analysis of antidepressants puts the discussion of these drugs back years.

The coverage was almost universally uncritical, and said little about the terrible adverse effects that some people can suffer while taking antidepressants, or while trying to get off them.

But there is nothing groundbreaking about this latest meta-analysis. It simply repeats the errors of previous analyses.

The analysis only looks at data for eight weeks of treatment, whereas in real life people often take antidepressants for months or even years. Few randomised, placebo-controlled trials have investigated long-term effects, but ‘real world’ studies of people treated with antidepressants show that the proportion of people who stick to recommended treatment, recover and don’t relapse within a year is staggeringly low (108 out of the 3110 people who enrolled in the STAR-D study and satisfied the inclusion criteria) (5). Moreover, several studies have found that the outcomes of people treated with antidepressants are worse than the outcomes of people with depression who are not treated with antidepressants (6;7), even in one case after controlling for the severity of the depression (as far as possible) (8).

Des Spencer, Hausarzt hat geschrieben:Antidepressants are still over prescribed!

I guess I am naturally skeptical. I have read this meta-analysis and its conclusion. Its conclusion is that in major Depressive illness antidepressants seem to work better than placebo by about 50% (the CIs are wide). This is hardly new, and a Cochrane review came to the same conclusion in 2009.[1]

The point is this. The average follow up is only 8-12 weeks, yet we have patients taking these for decades. What is the natural resolution of Depression? Why in this paper is there no mention of NNTs, just odds ratios?

It seems likely to be the same as before at around 9. [1] Therefore the vast majority of people being prescribed antidepressants do not benefit.

Also this is major depressive illness not typical of primary care. But medication will be prescribed in less severe cases without good evidence of benefit. Talk based treatments work better and should be first line. The problems linked to antidepressants are much higher than are reported. [2] Where is the research on long term data of efficacy and safety of antidepressants?

The suggestion from the authors that we should prescribe more antidepressants is simply wrong and not supported by the evidence.

Antidepressiva sind besser als ihr Ruf


Eine große Analyse zeigt, dass die 21 gebräuchlichsten Antidepressiva ausnahmslos wirksamer sind als Scheinmedikamente. Allerdings ist ihr Effekt eher gering bis moderat.
Die Mittel sind überwiegend gut verträglich.
Experten loben die Qualität der Studie, betonen aber, dass Patienten sehr verschieden auf Psychopharmaka reagieren.

Während Psychiater in einem begleitenden Kommentar loben, dass es nun bessere Daten gebe, um das optimale Antidepressivum für die Kranken zu finden, mahnen andere Experten, diese statistischen Erkenntnisse nicht überzubewerten. Wirksamkeit und Verträglichkeit können von Patient zu Patient unterschiedlich sein, sagt Klaus Lieb, Direktor der Klinik für Psychiatrie und Psychotherapie an der Universität Mainz. Bis heute können Mediziner nicht vorhersagen, wer wie auf welches Medikament anspricht. Manchen Patienten hilft gar keines dieser Mittel. Zudem hat die Studie nur die Wirkung in den ersten acht Wochen einer Depression untersucht. Was langfristig hilft, lässt sich damit nicht beantworten.

David Healy, Professor of Psychiatry at Bangor University, accused the authors of ‘hyping the benefits but hiding the harms’.

Antidepressants carry a risk of side-effects ranging from loss of libido to disabling anxiety and agitation. Other studies have shown that in rare cases they can trigger suicidal and homicidal thoughts.

Professor Healy said the short-term nature of the study, which looked at how patients responded after eight weeks, does not provide an accurate reflection of how most people take the drugs. ‘

'You could put alcohol through these trials and show it is an antidepressant,’ he told The Mail. ‘But it wouldn’t be a good idea to have 10 per cent of the population taking alcohol.’

He criticised the study, which looked at 120,000 patients from more than 500 trials — some of which had been funded by pharmaceutical companies — for failing to address the risks of long-term use.

While not officially classed as addictive, Professor Healy said the side effects of withdrawal were so severe, many patients end up taking them for long periods.

‘The problem is more that what a lot of people are going to be hearing from this is that the drugs work really well, when they don’t, and there are no harms being talked about. People assume they are safe, but they can be extremely risky.


‘About 80 per cent of people who get put on these pills by a GP will be on them for over a year and that will be because they can’t get off them.’

Last night, lead researcher Dr Andrea Cipriani admitted there were limitations to the Oxford study and that more research was needed to ensure patients were being effectively matched to treatments.

Potential risks and side-effects were not part of this review, he added. ‘Medication should always be considered alongside other options, such as psychological therapies, where these are available,’ he said.

However, Dr James Davies, from the Council for Evidence-based Psychiatry, said the work simply supports what has been known for a long time — that various drugs can have an impact on mood, thoughts and motivation.

‘The study does not bury the controversy around the damage caused by unnecessary long-term prescribing and will unfortunately do nothing to help reduce this.’

Here’s why the new study doesn’t tell us much new. The authors, Andrea Cipriani et al., conducted a meta-analysis of 522 clinical trials looking at 21 antidepressants in adults. They conclude that “all antidepressants were more effective than placebo”, but the benefits compared to placebo were “mostly modest”. Using the Standardized Mean Difference (SMD) measure of effect size, Cipriani et al. found an effect of 0.30, on a scale where 0.2 is considered ‘small’ and 0.5 ‘medium’.

The thing is, “effective but only modestly” has been the established view on antidepressants for at least 10 years. Just to mention one prior study, the Turner et al. (2008) meta-analysis found the overall effect size of antidepressants to be a modest SMD=0.31 – almost exactly the same as the new estimate.

Cipriani et al.’s estimate of the benefit of antidepressants is also very similar to the estimate found in the notorious Kirsch et al. (2008) “antidepressants don’t work” paper! Almost exactly a decade ago, Irving Kirsch et al. found the effect of antidepressants over placebo to be SMD=0.32, a finding which was, inaccurately, greeted by headlines such as “Anti-depressants ‘no better than dummy pills‘”.

The very same newspapers are now heralding Cipriani et al. as the savior of antidepressants for finding a smaller effect…

Typische Nebenwirkungen der modernen Wirkstoffe wie etwa Mundtrockenheit, Kopfschmerzen, innere Unruhe oder vorübergehender Libidoverlust können unangenehm sein, sind aber bestimmt den Symptomen einer Depression vorzuziehen. Bei somatischen Medikamenten nehmen Patienten vergleichbare Effekte achselzuckend in Kauf.

Die Lancet-Studie könnte dazu beitragen, diesen Streit endlich mal zu beenden. Sie zeigt erneut, dass Antidepressiva zwar keine Wunderpillen sind, aber vielen Betroffenen leidlich helfen. Sie wirken ähnlich gut wie etwa Triptane bei Migräne.

„Antidepressiva sind leider keine Medikamente, die besonders gut wirken, und man muss sie sehr lange einnehmen“, betont Gartlehner. „Und nur rund 60 Prozent der Patienten sprechen überhaupt darauf an“, sagt er.

Alle Triptane haben ihre Wirksamkeit und Sicherheit in großen placebokontrollierten Studien mit gut vergleichbarem Design bewiesen. Laut den Ergebnissen der Zulassungsstudien können Triptane rund 60 Prozent der Patienten helfen, die auf NSAR/Analgetika nicht ansprechen. In den späteren Beobachtungsstudien waren es bis zu 90 Prozent der Patienten.

The reaction to the Lancet’s antidepressant effectiveness study: an attempt to spin a sow’s ear into a silk purse

On the 21st February, 2018, a study addressing the effectiveness of antidepressant drugs was published in The Lancet. It has caused quite a stir. Accepting the subsequent media headlines at face value, one would be forgiven for believing that a cure for all human misery had been confirmed and that emotional distress and suffering could now be eradicated from our planet. Across TV screens, newspapers and the social media, representatives of the psychiatric establishment, together with its followers wedded to the illness-like-any-other approach to human suffering, typically displayed a mix of glee and self-righteousness. The central message was that all those pesky critical people who had dared to suggest that antidepressants are overprescribed, minimally effective and doing more harm than good had been proved wrong and should now be silenced.

Further reflection on the Lancet study, and the reaction to it, leads to a very different conclusion: it represents a stark example of how to spin a mundane, predictable finding into something that sounds ground breaking.

A primary focus on doling out more antidepressants as a cure for human misery is misguided and unhelpful. Medicalising distress and suffering in this way will only benefit those privileged groups who currently gain advantage from this ‘illness like any other’ approach: the pharmaceutical industry and the psychiatry profession. The findings of the Lancet study do not change this assertion.

Murmeline hat geschrieben: ↑26.02.2018 20:19

an attempt to spin a sow’s ear into a silk purse