HAPPY EVER AFTER?

IT'S NEW York in 1988. America is depressed and the psychiatrist's
couch, so beloved of Freudians and Woody Allen movies, is beginning to
wear a little thin.

Psychotherapy is at last going out of fashion as it is discovered that
it is not, after all, very effective in lifting moods and curing
depression. As for drugs, those available date back to the Second
World War and are not popular in a culture which idolises novelty.

The opportunity was there for something new and one drug company felt
it had the answer - the zappily named Prozac. It was brand-new, it was
different, it had reportedly fewer side-effects than previous pills.
Surely it was what America and the world was crying out for, sometimes
literally.

As we now know, it was to be hugely successful - accounting last year,
in Scotland alone, for UKP10 million of the NHS drugs budget. Rewind
to Indianapolis in 1972. Dr Ray W Fuller, a biochemist specialising in
neuroscience, and his colleagues, Dr David Wong and Dr Bryan Molloy,
were among many scientists desperate to find a new generation of
antidepressants which would satisfy society's demand for a pill to
take the place of older drugs, the tricyclics whose unpleasant
side-effects, including weight gain, dry mouth and blurred vision,
made people reluctant to take them, thus reducing their
effectiveness.

Working in the laboratories of the pharmaceutical company Eli Lilly,
they took a different tack, exploring compounds which would increase
the levels in the brain of a naturally occurring substance, serotonin,
which is one of the neurotransmitters which carries signals between
nerve cells. At the time, it was suspected, although not proved, that
very low levels of serotonin could lead to depression. The team
discovered a compound called fluoxetine hydrochloride, one of a class
of drugs which was to become known as selective serotonin reuptake
inhibitors (SSRIs). These compounds increased the levels of the
chemical in the brain by preventing the cells that release it from
reabsorbing it too quickly.

It worked in the laboratory, but extensive testing had to follow.
Clinical trials did not begin until 1976, which was a full ten years
before the drug gained its first licence.

Against a background of increasing public awareness of the
side-effects and/or addictive nature of other drugs, including
tranquillisers, no drug company was going to release such a
revolutionary new treatment without putting it through the most
stringent of tests. In addition, there remained, as there does today,
some public hostility to drug treatments for depression, partly due to
the stigma which is still attached to mental illness.

Prozac was first approved for marketing in December 1986 in Belgium
and a year later received clearance from the powerful US Food and Drug
Administration. And ten years ago the first NHS prescriptions for the
new "wonder drug" were filled in Britain.

"I was working in the States just before Prozac came along and America
was certainly ready for it," says Dr Cosmo Hallstrom, a spokesman for
the Royal College of Psychiatrists and the medical director of the
Charter Clinic in Chelsea. "At the time they were still into Freudian
analysis, which is not very good for depression. This drug was some
thing that was new - Americans like things which are new - and it was
a quantum leap in efficacy from what they had before. Then it made the
cover of Time magazine and spilled out to the rest of the world."

Nobody could have foreseen how the drug would capture the popular
imagination. Books were published, extolling the virtues of the
green-and-white capsule, including Elizabeth Wurtzel's Prozac Nation
and Peter Kramer's Listening to Prozac. Just as the word "Hoover" has
become synonymous with "vacuum cleaner", so did Prozac come to mean
anti-depressant to a growing majority. Wurtzel almost became to
epitomise the drug's growing designer image, even posing topless on a
loo for the style magazine GQ. According to one pharmaceutical
insider, Prozac became the acceptable face of mental illness. It came
to the point where the accessories of a successful person would
include a designer suit, Filofax and Prozac.

OUTLANDISH claims were made for the drug, with many saying it released
creativity and helped artistic performance. That respected forum for
the chattering classes, The Late Show, even used its cultural
television slot to test out these claims, giving a number of artistic
types the drug then sending them off to see how creative they could
be. The results of this experiment were unfortunately inconclusive, as
the judges could not decide how "creative" the participants would have
been without chemical help.

"I think Prozac has helped raise awareness about depression," says
Rodney Elgie, the executive director of the Depression Alliance. "I
suppose in the Eighties depression was like cancer in the Sixties,
something that just wasn't mentioned. Prozac may have helped a bit,
although there is still a stigma attached to depression ten years
after the drug was launched."

Elgie warns that the drug is open to what he calls abuse, citing
America in particular, where it is possible to order the drug by
e-mail, not for depression but because it is alleged to improve
performance generally.

But most GPs and psychiatrists in Britain would argue that this is not
the case in Britain. Dr Kenneth Harden, who chairs the British Medical
Association's GP committee, says: "The mythology grew up in America
that Prozac is the happiness drug. It's not. Prozac is really only
effective in people who are clinically depressed."

Harden believes the greatest difficulty is not turning away hosts of
mildly dissatisfied people who believe Prozac might be their key to
happiness - rather, it's persuading people who are depressed that a
pill will help, that it will take time to work and even, that they are
depressed. If anything, he believes there are not enough
antidepressants prescribed in Scotland, not because GPs are unwilling
but because patients do not want to take a pill.

Hallstrom in London has found the opposite in some ways. "We're a
pill-popping society. We go out drinking then take a pill the next
morning to make our headache go away, we smoke, then get chest
infections, so we take antibiotics to make them go away and in sex we
take pills to prevent pregnancies.

It should be normal for people to feel that if they have a serious
illness and a pill can help, then they should take it."

Hallstrom believes depression is under-diagnosed in Britain, and
claims some of his patients only realised they were depressed after
taking Prozac. He too believes there is still a stigma attached to
mental illness, despite Prozac's success in raising public awareness.
"In the States you would go to dinner parties and everyone would be
talking about what their therapist had said. That really doesn't
happen here."

Analysts find it difficult to account for Prozac's extraordinary
success in becoming a highly recognisable brand name. "Presumably it
was very well marketed to GPs who would then prescribe it to their
patients," says Wally Olins, founder of branding consultants Wolff
Olins. "And success is self-perpetuating in a way. As more people hear
about it, then more doctors will think it is safe to prescribe. It
might have been the first on the market but this does not mean it will
be the most successful - very often the first don't get all the
success because they have been so busy pioneering."

So it could just be that Prozac simply captured the spirit of the age.
As Hallstrom says, America was ready, the rest of the world followed.

AND the drug did work. As the researchers had hoped, the SSRIs proved
to have fewer unpleasant side-effects than the old-style
antidepressants. The new drugs were also safer, in that it was harder
to overdose on Prozac than on tricyclics. No drug is completely clean,
however, and soon even the "sunshine" pill hit a backlash. Sexual
dysfunction was perhaps the most publicised side-effect, nausea was
another. The drugs also took some time to kick in, although the
side-effects were apparent right away.

Patients therefore had to endure up to several weeks of debilitation
before they started to feel better. Then, even worse, Prozac was
linked with violence and suicide. In one case, in which a Kentucky man
went on a shooting spree in a Louisville printing plant, survivors and
victims' families sued Lilly, blaming Prozac for the gunman's violent
behaviour.

The jury found in Lilly's favour in 1994, but since then, others have
claimed in court that Prozac was the reason behind the actions which
brought them there. More books have been published, this time
detailing the hell Prozac had put people through and support groups
have been set up. A quick check on the Internet shows the supporters
and detractors matched virtually site for site. For every Van Gogh
claiming the drug untapped his creativity there is a writer claiming
Prozac ruined lives.

And while nobody can doubt the success of Prozac as a product - it has
been used by 35 million people worldwide - other, newer SSRIs are
doing more than snapping at its heels. One of these drugs is Seroxat,
launched a couple of years after Prozac, by SmithKline Beecham. A
spokesman says Prozac's higher profile has not harmed his company's
product. "In 1997 Seroxat captured a massive share of the market and
it is the fastest-growing antidepressant. Prozac was the first SSRI
and obviously was very successful, but better drugs have come along."

But there is nobody resting on laurels. Drugs companies are already
working on "sons of Prozac", new products which might provide the
benefits without the current problems. A pill whose benefits would
kick in quickly, where side-effects were minimised, a pill, which
perhaps had to be taken only once a week, or for less than the usual
six months. The market is certainly there.

According to Elgie, there are four million people suffering from
depression at any one time. According to Harden, depression is the
single biggest cause of GP consultations in this country. And is it
coincidence that Prozac's growth has mirrored the gradual willingness
of people in Britain to admit they might have a problem? Hallstrom
says: "There has been an explosion in counselling and people are now
much more likely to be prepared to talk about what's wrong. And
there's certainly a lot of it about."