For better or worse, what the public knows about depression is largely due to massive investment by the pharmaceutical industry in the years following the launch of Prozac in 1988.
Before Prozac, depression was treated with older Tricyclic Antidepressants (TCAs) or Mono Amine Oxidase Inhibitors (MAOIs). While these drugs were relatively effective in the treatment of depression, they came with a series of side effects and risks that stood in the way of their being used in all but the most severe cases of depression. TCAs, for example, are highly toxic in low overdose – making them thoroughly unsuitable for a group of people at significant risk of suicide. MAOIs are contraindicated with a range of drugs and foods, making safe compliance difficult. Prozacwas at least as effective, and came without the dangerous side effects of these drugs.
Prozac was the first Selective Serotonin Re-uptake Inhibitor (SSRI) to attract significant marketing investment (at the height of the SSRI boom in the early 2000s, pharmaceutical companies were spending twice as much on marketing as on research). The success of Prozac spawned a raft of "me too" SSRI drugs. Research was also carried out on drugs that promoted levels of other neurotransmitters such as Noradrenaline, leading to SNRI and SSNRI antidepressants in the early 2000s.
One of the ways in which pharmaceutical companies marketed their antidepressants was to fund patient information initiatives. In the UK, this wasn't done to promote a particular drug (direct advertising of medicines to the public is illegal), but simply by raising awareness of the condition. The UK National Depression Campaign in the 1990s was underwritten by the pharmaceutical industry, and involved the funding of several mental health charities to promote the importance of seeking medical help for depression.
Although the main aim of this funding was to sell antidepressants, its by-product was increased public awareness of depression. This, in turn, paved the way for scientific and public discussion of the alternatives to antidepressants – one of the reasons that the UK government is rolling out Cognitive Behavioural Therapy (CBT) throughout England is that psychologists adopted the same campaigning methods as the pharmaceutical industry in order to promote CBT as the alternative to antidepressants.
Of course, any boom is followed by a bust. For SSRI antidepressants, this came in 2003 as the dangers of side effects and withdrawal symptoms became headline news. Fears about the risk of suicide in younger users led to restrictions on all but Prozac for this group.
Fears about side effects coincided with a concern that pharmaceutical companies and the charities they provided funds to were "disease mongering" – encouraging increasing numbers of us to be diagnosed with depression in order to push up antidepressant prescribing. This seemed to be born out by big increases in antidepressant prescribing (although this was actually due to changes in prescribing practices). It was exacerbated by claims that a quarter of the population has mental illness with around 22% of people experiencing depression (the actual figure for diagnosed mental illness is 1 in 10 people in any year).
Despite allegations of "disease mongering", the pharmaceutical companies made most of their profits in the 2000s by influencing changes in government guidance to GPs, requiring them to keep patients on antidepressants for longer (and sometimes for ever) and to withdraw patients gradually. Taken together, these two changes would double the length of time a patient was prescribed an antidepressant. Because of the significantly higher cost of the low-dose versions of antidepressants used in gradual withdrawal, this created more than double the profits.
Most pharmaceutical companies in the antidepressant market had followed up on the success of SSRIs with the creation of second generation SSRIs and SNRIs such as Efexor and Escitalapram. Marketing investment for these continued into the late 2000s. However, competition from generic versions of the early SSRIs was beginning to affect the rate of profit. NICE guidance on antidepressant prescribing requires GPs to begin treatment using older SSRIs such as fluoxetine (generic Prozac) and citalopram (generic Cipramil) which can cost less than £2.00 for a month's supply.
The financial crash in 2008 forced public authorities to make dramatic cuts in spending on medication. With public spending likely to be dampened for a decade, this spelled the final nail in the coffin of antidepressant research. What research there has been in recent years has tended to be in the form of "me again" research. This involves finding (and licensing) new uses – e.g., pain management or menopause – for existing antidepressants.
The cost of developing new medicines has been increasing dramatically in recent years. In 1979, it cost just 54m US dollars to bring a drug to market. By 2003, this had risen to $897m. This means that pharmaceutical companies are reluctant to re-invest in drugs aimed at illness where effective treatments are already available.
In November 2011, when Astra Zenica's trial TC-5214 failed to show a benefit in phase III trials (making it highly unlikely to ever be licensed as an antidepressant), it effectively marked the end of research into new antidepressants. Astra Zenica is committed to completing the trials into TC-5214. But that's it! Everyone else has moved on.
The only new antidepressants on the horizon are generic versions of existing drugs. However, growing use of generic drugs further cuts the profits made by those companies that have – until now – been funding research into improved antidepressants.
Users may reasonably complain that "antidepressants don't work". Sure, they "benefit" 60-70% of users. But "benefit" is not the same as "cure". They come with side effects and withdrawal symptoms that can be disabling in their own right. Nevertheless, they are "part of the solution" to depression for millions of people worldwide. Moreover, alternatives such as talking therapies are proving far too expensive to be a publicly-funded alternative. But existing antidepressants are far from ideal (and the jury is still out on the health impact of long-term use). People with depression really could do with more research.
Had we (i.e., the politicians) been cleverer, we would have negotiated contracts that required pharmaceutical companies to reinvest a proportion of the profits made on licensed drugs on research into new drugs. We didn't. And for better or worse, for millions of people with depression worldwide, this means that there are not going to be any new, improved antidepressants.