SSRI antidepressants can cause permanent harm

What are the benefits of psychotropic drugs?

BERLIN. Electroconvulsive therapy (ECT) is still undisputedly the most effective therapy for severe depression. It is essentially based on a disruption of psychopathological processes: the generalized seizure that is triggered apparently acts like a cleansing thunderstorm and blows away even the darkest thoughts.

When the brain is then restarted, the organ flooded by various neurotransmitters often enters a less pathological state. Whether one explains the effect of ECT one way or another, there should be agreement that the method is more brutal than specific.

Now that the past 90 years of psychopharmacological research have produced nothing that can rival the antidepressant effects of ECT, the question arises as to how specific and effective antidepressants in particular and psychotropic drugs in general are. There were also critical voices at this year's DGPPN congress. Some experts are of the opinion that many of the drugs used in psychiatry do more harm than good to patients in the long term.

No better than exercise in the fresh air?

One of the best-known antidepressant critics is undoubtedly the psychologist Professor Irvin Kirsch from Harvard Medical School in Boston. With his meta-analyzes he repeatedly puts his finger in a festering wound: The differences between antidepressants and placebo are quite small in most studies.

Kirsch does not question the significantly better effectiveness of the antidepressants compared to placebo, but considers them to be clinically irrelevant. Due to possible side effects such as gastric bleeding, sexual dysfunction and insomnia, their use is only justified in severe depression. In his opinion, patients should rather be treated psychotherapeutically.

At the DGPPN congress, Kirsch went one step further: more than 80 percent of the antidepressant effectiveness is based on the placebo effect. In the meantime, this has also been shown by a number of meta-analyzes from other working groups. None of them could prove a clinically significant effectiveness for antidepressants according to the British NICE criteria.

Look for a non-arbitrary criterion of effectiveness

This requires a verum-placebo difference of 3 points on the Hamilton Depression Scale (HAM-D). In his analyzes from 2002 and 2008, Kirsch found a difference of only 1.8 points. Exactly the value that an FDA analysis of over 23,000 individual patients has now shown. Kirsch does not accept criticism that the NICE criterion was set arbitrarily: "This also applies to the definition of the response rate as at least 50 percent symptom reduction or the statistical significance with a p-value below 0.05."

What, according to the psychologist, could be a non-arbitrary effectiveness criterion? He tried the overall clinical picture (CGI). A difference of up to 3 HAM-D points is assessed by doctors as "no change". In some studies, the HAM-D value under antidepressants has now been reduced by up to 14 points, which is rated as "greatly improved".

Effect also in placebo patients

As a rule, however, the placebo patients would also have improved significantly or greatly in such studies. From the overall clinical impression, no clinically better efficacy can be derived than with placebo.

Kirsch also complained that in antidepressant studies around 80% of the patients who usually received such drugs in practice were excluded. Instead, he referred to the practical STAR * D study: Here the HAM-D value decreased by only 6.6 points on average under antidepressants, which corresponds to only a slight improvement in the CGI.

The psychologist also cited an analysis from 2012 according to which antidepressant treatment did not reduce symptoms more than psychotherapy, acupuncture or exercises in the fresh air.

Increased recurrence rate after discontinuation of antidepressants

However, Kirsch considers the increased recurrence rate after discontinuation of antidepressants to be particularly problematic: In studies, around half of the participants on SSRIs became depressed again in the first six months after discontinuation, but only 20-30 percent after discontinuation of placebo and after About a third at the end of psychotherapy.

In a study from 2000, the relapse rate in a group with physical training was only 8 percent after ten months; if patients had also received an SSRI during training, it was 31 percent. Kirsch suspects that there is a significant rebound effect after discontinuing SSRIs.

Specific Effects - Just a Myth?

The British psychiatrist Dr. Joanna Moncrieff explores the effectiveness of antipsychotics and antidepressants. She does not see sufficient evidence for serotonergic disorders in depression or for dopaminergic dysfunctions in psychoses. In her current book "The Bitterest Pills" she doubts that psychotropic drugs even specifically restore a disturbed transmitter balance.

In their opinion, antipsychotics only shut down brain systems that are also needed for psychoses. A disruption, as brutal as the ECT, only medically.

Moncrieff speaks here of a drug-based effectiveness: A psychoactive substance shows a certain effect in the brain, which also has an effect on the psyche. Alcohol relieves social anxiety because of its disinhibiting effects, but there is no specific effect of alcohol on these anxieties.

Attenuation of vegetative reflexes

In a similar way, a strong sedative can also relieve psychosis because it also dampens states of arousal. In other words: if you switch off central functional areas, you also reduce psychological symptoms. However, this is miles away from a specific effectiveness such as that shown by insulin.

They believe that most psychoactive substances only change normal mental status - with effects on the psyche. The psychiatrist recalled that the first antipsychotics such as chlorpromazine were initially introduced as special sedatives, as "neurological inhibitors", and only later were they given the name "antipsychotics", which suggests a specific effect on psychoses.

In fact, like alcohol, such drugs would have a whole range of effects: They slow down physical activity, attention, reaction time, coordination, spontaneous activity and paralyze the memory, they sedate, lead to emotional flatness and indifference. The original term "neuroleptics" is therefore more appropriate: substances that dampen vegetative reflexes and relieve psychological tension.

Harm can outweigh benefit

"A constant fog of lethargy and indifference. I just wanted to sit around and eat," Moncrieff quoted a patient as having an atypical condition. Nonetheless, many patients would prefer this condition to psychosis and would be happy to have the medication.

The psychiatrist pointed out, however, that with long-term therapy the harm could outweigh the benefit - even with atypical neuroleptics. In a long-term analysis over 20 years, patients who did not take such drugs on a long-term basis performed significantly better in terms of social function than those on long-term therapy: They had more jobs, fewer relapses and more symptom-free periods.

This cannot only be explained by a selection bias. In a randomized study, patients on long-term therapy fared significantly worse after seven years than those in whom the medication was discontinued or reduced after the end of the acute phase: their level of social function was significantly impaired. Interestingly, the recurrence rate after discontinuation doubled in the short term, but not increased in the long term. If you consider the risk of extrapyramidal disorders or increased brain volume loss under antipsychotics, it is very questionable whether the drugs are suitable for long-term therapy, explained Moncrieff.

"How desperate do we have to be?"

But what are the alternatives? Apparently it looks bleak here. Professor Gerhard Founder from the University of Aachen showed a 100-year-old photo of mentally ill people in ice baths at the congress. With this shock therapy one tried at that time to help depressed people.

They are heated today, he said, referring to a recent publication on hyperthermia treatment. "What are we actually doing here? How desperate do we have to be? Nobody seriously believes that hyperthermia has a specific antidepressant effect."

Founder named a number of other shock treatments that had achieved dubious fame in the past, such as insulin coma and lobotomy. "At best we are disturbing the brain function." The psychiatrist is similarly critical of experiments with psilocybin and ketamine. "Isn't ketamine the best pharmacological model for schizophrenia, and with this of all things we hope to achieve a better antidepressant effect than with previous drugs?"

New endpoints for long-term studies!

In our desperation, said the founder, we should use any means to disrupt brain function and push the Hamilton score down a few points. However, nobody can say how long the effect will last and what long-term consequences will be accepted.

He therefore called for long-term studies and new endpoints that also take quality of life and psychosocial functioning level into account. This is the only way we can determine whether we have progressed beyond the level of shock therapy.