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New research suggests antidepressants don’t work for many people because they’ve been targeting the wrong thing.
The research seems to suggest that stress is not a major cause of depression and that it is not caused by an imbalance in neurotransmitters.

The research was carried out on rats and certainly the first finding about stress does seem rather counter-intuitive, particularly given previous research such as this study reported in The Independent linking high-stress jobs with depression.

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6 Reasons To Be Skeptical

That’s right! A study in this month’s American Journal of Psychiatry was written up by the BBC yesterday–not sure if there was a report on the radio or TV–and framed as establishing that anti-depressants work “instantly” to quote the BBC’s headline. That would run counter to what most researchers and patients believe to be true (and plenty of studies have shown to be true) that anti-depressants take as long as several weeks to deliver a measurable effect. What Oxford researchers found was that depressed patients had a quick response to an anti-depressant called Reboxetine. They established this by measuring how patients’ negative thoughts improved (using emotional recall kinds of tests) and found that negative thoughts improved within a few hours and even did so in healthy, non-depressed volunteers taking the drug.

“Dr Harmer said: ‘We found the antidepressants target the negative thoughts before the patient is aware of any change in feeling subjectively.’

“‘Over time, this will affect our mood and how we feel because we are receiving more positive information.’”

Michael Thase, a psychiatry professor at the University of Pennsylvania, called the finding possibly “paradigm changing.”

We live in interesting times when researchers can claim an anti-depressant is “working” when a patient has no sign of depression symptom improvement. As usual, several skeptical thoughts come to mind.

1. You don’t know you are feeling better but you are is one of the study’s main conclusions. That strikes me as a dubious claim, especially absent any knowledge of how the patients and healthy volunteers fared over time. I mean, isn’t the point of treating depression to treat depression and not get all wound up about emotional recall tests? To the degree that it might predict later response to depression treatment, the response might be interesting.

2. The choice of Reboxetine (brand name Vestra) is an odd one. A recent study found it the least effective of all the modern anti-depressants and the FDA has not approved it for use in the US (which tells you something) and it’s not widely-used in Europe. Why the researchers didn’t choose a more commonly used medication is beyond me. It really doesn’t tell doctors and patients much in a clinically useful way.

3. The study is of a small enough sample size–31 depressed patients, 30 healthy volunteers; half of each group on active medication–to make its findings little more than suggestive and not the paradigm changer Thase claims. It’s research that needs to be replicated several times.

4. I’m not buying that someone on Reboxetine identifying more faces (two more on average) on a facial recognition test than someone not on Reboxetine means that much in a real world way. Maybe I’m being too skeptical here, but it doesn’t quite add up.

5. The study’s two primary authors (Guy Goodwin and Catherine Harmer–interesting name for a doc) have oddles of pharma funding in their past from the likes of AstraZeneca, BMS, Lilly and so on.

6. For the BBC to generalize from results of a Reboxetine study that its findings apply to all anti-depressants is complete bunk and lazy reporting and editing. And that’s pretty much what the article and its headline claim.

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During 1993-2004, the number of UK patients newly-diagnosed with depression declined by nearly 25%, but numbers of prescriptions written for antidepressants nearly doubled in the same period, says a new study.

This dramatic rise is due to a year-on-year increase in the number of people taking antidepressants on a long-term basis, researchers from the University of Southampton conclude, in a study published the British Medical Journal (BMJ) on October 23.

The researchers extracted data on all new incident cases of depression from the general practice research database (GPRD) between 1993 and 2005 and, analysing data from the 170 practices that contributed for the full duration of the study, they found that a total of 189,851 people experienced their first episode of depression between 1993 and 2005, of which 150,825 (79.4%) received a prescription for antidepressants in the first year of diagnosis. This proportion remained stable across all the years examined.

The overall incidence of new cases increased in young women but fell slightly in other groups, such that overall incidence increased then declined slightly; men – 7.83 cases per 1,000 patient years in 1993 to 5.97 in 2005; women – 15.83 cases per 1,000 patient years in 1993 to 10.06 in 2005. However, antidepressant prescribing nearly doubled during the period, the average number of prescriptions issued per patient rising from 2.8 in 1993 to 5.6 in 2004, and the majority were given as long-term treatment or as intermittent treatment to patients with multiple episodes of depression.

According to data from the NHS Prescription Services (NHS RxS), more than 30 million prescriptions for selective serotonin reuptake inhibitors (SSRIs) including Eli Lilly’s Prozac (fluoxetine) and GlaxoSmithKline’s Seroxat (paroxetine), are now issued per year, twice as many as the early 1990s, and the researchers found that 90% of people diagnosed with depression are now taking SSRIs either continuously or as repeated courses over several years.

“We estimate that more than two million people are now taking antidepressants long-term over several years, in particular women aged between 18 and 30,” said the study’s leader Tony Kendrick, professor of primary medical care at the University’s School of Medicine.

Moreover, he noted the team’s previous research had found that while these drugs are claimed not to be addictive, many patients had in fact found it difficult to come off them, due to withdrawal symptoms such as anxiety, and many wanted more help from their general practitioner (GP) to come off the drugs.

“We don’t know how many really need them and whether long-term use is harmful. This has similarities to the situation with Valium in the past,” said Prof Kendrick.

Commenting on their findings, the researchers conclude that, while previous clinical guidelines have focused on antidepressant initiation and appropriate targeting of antidepressants, future research and guidance should, in order to address the costly rise in prescribing of these drugs, concentrate on appropriate long-term prescribing for depression and regular review of medication.

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In the second part of the study, Redei found strong indications that depression actually begins further up in the chain of events in the brain. The biochemical events that ultimately result in depression actually start in the development and functioning of neurons.

“The medications have been focusing on the effect, not the cause,” she said. “That’s why it takes so long for them to work and why they aren’t effective for so many people.”

Her animal model of depression did not show dramatic differences in the levels of genes controlling neurotransmitters functions. “If depression was related to neurotransmitter activity, we would have seen that,” she said.

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