In early February, the newspapers jubilantly announced the end of the search for a magic bullet that would successfully treat the depression and anxiety that affects an estimated one in four women and one man in eight at some point in their lives.
SmithKline Beecham launched a new drug that they claim is highly effective with none of the side effects of the old antidepressant drugs the monoamine oxidase (MAO) inhibitors and the tricyclics (also known as the antipsychotic drugs).The drug, paroxetine, marketed here as Seroxat and in the States as Aropax, is a new category of drug called a "selective serotonin uptake inhibitor", or a 5HT drug. One cause (or outcome) of depression and suicidal behaviour is believed to be low levels of a brain chemical known as serotonin, or 5HT. Paroxetine works by increasing the availability of serotonin in the brain by slowing the passage of this neurohormone into nervous system cells. According to The Pill Book by Harold M. Silverman (Bantam), this type of drug takes about four weeks to work, and stays in the body several weeks after you stop taking it.
In a press release (handed out for "the attention of accredited medical correspondents only", whatever that means) SmithKline Beecham noted several advantages of Seroxat over the older tricyclic antidepressants. These include (and we quote):
Effective therapy for patients who can return to a normal, economically active life because Seroxat is highly selective and more precise in action than other antidepressants.
Effective treatment of anxiety and sleep disturbance often associated with depression.
Enhancement of the patient's quality of life. Seroxat does not cause sedation, or impair thinking or physical activity, nor does it have a stimulant or alerting effect. Thus its neutral effects in this regard distinguish it from other available antidepressants.
Fewer side effects and excellent tolerability, compared with the older tricyclic antidepressants, which enhances compliance and enables more patients to benefit from the treatment.
Enthusiasts are already planning to widen the uses of paroxetine for migraine or overweight patients, those with cancer experiencing nausea from anticancer drugs, and people with obsessive compulsions, like handwashing. And because there is some evidence that this kind of drug reduces dependence (unlike the benzodiazepines) by stimulating the reward mechanism in the brain, doctors are discussing the possibility of using paroxetine to help control smoking and dependence on other drugs.
The Financial Times assured readers that paroxetine has far fewer side effects than the older anti depressants, comparing it with Eli Lilly's 5HT Drug, Prozac (fluoxetine). Launched three years ago and hailed in the media as the breakthrough medicine has been waiting for to treat depression, Prozac quickly became America's best selling anti depressive, with sales expected to reach more than lb500 million this year.
What the FT failed to report was what has happened in the States with Prozac and also the cautionary notes Eli Lilly has sounded in the American drugs bibleThe Physician'sDeskReference. Speaking on behalf of SmithKline Beecham, Alan Chandler assures us that paroxetine is not identical in chemical makeup to Prozac but more "selective in hitting the right centres of the brain". Although one cannot assume that Seroxat's side effects will be the same as those of Prozac, Chandler admits that there is a "similar spectrum" of side effects. Consequently it's worth looking at America's experience with its first 5HT drug before automatically running to your doctor for a prescription for this new one.
According to The Doctor's People (the American newsletter founded by the late medical critic Dr Robert Mendelsohn and until recently edited by its co-founder, Vera Chatz), numerous Prozac users are in the process of suing Lilly, claiming that the drug caused suicidal and homicidal thoughts and actions.
In one case, a Prozac user killed five and wounded l2 others at the printing plant where he worked. In another, a 40 year old New York secretary claimed that she became "obsessed with dying" and began harming herself with whatever sharp implements she could find.
Although there was no evidence of "suicide ideation or activity," with Seroxat, says Chandler, SmithKline Beecham, to his knowledge, did not test for an increase in homicidal tendencies.
In keeping with US regulations (and American drug company caution), Lilly has published page after page of warnings about potential side effects of Prozac. Some l0 to l5 per cent of patients in initial clinical trials reported having anxiety and insomnia and a "significant number", particularly underweight patients, report significant weight loss or anorexia. About l0 per cent of patients in clinical trials reported anxiety as a side effect and almost 9 per cent, anorexia. In other words, l in l0 patients, experience the same symptoms from the drug that they are trying to treat. In one study, says Silverman in The Pill Book, l3 per cent of patients on the drug lost more than 5 per cent of their body weight.
Although there was no significant change in body weight in the 4000 test subjects who took Seroxat for a year, SmithKline Beecham warns that the most common side effect includes insomnia. Again, the drug can cause one of the symptoms that you are trying to treat.
Prozac has also been known to affect nearly every system of the body, including nervous, digestive, respiratory, cardiovascular, musculoskeletal, urogenital and skin and appendages. These side effects include, most commonly, visual disturbances, palpitations, mania/hypomania, tremors, symptoms of flu, cardiac arythmia, back pain, rashes, sweating, nausea, diarrhoea, abdominal pain, loss of sex drive. Less common effects include antisocial behaviour, double vision, memory loss, cataracts or glaucoma, asthma, arthritis, osteoporosis, stomach bleeding, kidney inflammation and impotence. According to The Pill Book, fluoxetine also, albeit infrequently, causes "abnormal dreams, agitation, convulsions, delusions and euphoria."
The side effects reported by SmithKline Beecham about Seroxat include nausea, somnolence (drowsiness), sweating, tremor, asthenia (loss of physical strength), dry mouth, and sexual dysfunction. And although the company boasts that this drug is not addictive, they recommend that patients be weaned off the drug gradually "as abrupt or sudden discontinuation may lead to symptoms such as disturbed sleep, irritability or dizziness". The company also warns that it shouldn't be used by patients with a history of mania.
Both drugs have side effects when taken with other psychoactive drugs. Prozac interacts with numerous other drugs and should not be taken with them. For instance, it may prolong the effects of benzodiazepines like Valium and increase the action of warfarin, used to treat blood clots, and digitalis preparation digoxin, for congestive heart failure and cardiac arrhythmias. Patients taking Prozac with tryptophan can become agitated with upset stomachs.
SmithKline Beecham warns that Seroxat should not be taken in combination with MAO inhibitors (or even two weeks after finishing treatment with them, and vice versa), oral anticoagulants, tryptophan, drugs affecting liver metabolizing enzymes, lithium, anticonvulsants and warfarin.
The innumerable side effects now associated with Prozac raise the question of whether depression can be successfully treated by any drug at all. MIND, the association for mental health, terms administering a drug for depression "biological reductionism" a poor substitute for the loving care of friends, the professional counselling and the individual's development of the inner resources required to combat any depression that is not purely physical in origin.
Depression is oftentimes an utterly appropriate response to a sudden life crisis, such as divorce, death of a loved one, loss of a job. Depression is usually defined as emotional shock a sadness so profound that it impairs normal functioning. Some of the accompanying symptoms include: difficulty concentrating, thoughts of suicide, changes in sleeping habits (decreased or increased need for), changes in weight (gain or loss), feelings of being out of control, self castigation and guilt. A drug may help someone to cope for a short time, but it cannot replace the simple process of coming to terms with the loss.
In many cases, depression can be caused by other drugs. According to the Health Research Group, the American Ralph Nader founded lobby organization, depression can come on after the introduction of certain drugs. Fifteen categories of drugs can bring on depression, including barbiturates, tranquillizers, beta blockers, heart drugs, particularly those containing reserpine, drugs used to treat cardiac arhythmias, ulcer drugs, high blood pressure drugs, corticosteroids, antiparkinsonian drugs, amphetamines, painkillers, arthritis drugs, anticonvulsants, antibiotics, and drugs to treat slipped discs or alcoholism. (see box, p 3 for HRG's specific listing of drugs). If your feelings of depression have come on about the time you started on a new drug, look first to that drug as the cause.
Unfortunately, in too many cases, the treatment for drug induced depression unrecognized as such is an antidepressive, which can react with the original drug and cause further physical or mental problems. The only treatment for this kind of depression is to stop or gradually cut down on the original drug or, if absolutely necessary, to switch to a similar acting drug that will not cause depression.
Certain illnesses can also bring on depression. In Worst Pills, Best Pills, the HRG says that several medical conditions can cause depression. These include problems with thyroid, certain cancers (pancreatic, bowel, lymph node or brain), hepatitis or viral pneumonias, strokes, or Parkinson's or Alzheimer's disease. In the case of Parkinson's, both the illness and the "cure" (antiparkinsonian drugs) can bring on depression. In many self limiting diseases, antidepressant drugs will only create new illnesses.
The older antidepressant drugs also carry a host of side effects. In case this puts you off the newfangled drugs and makes you opt for the tried and tested tricyclic drugs, they have their own problems. These include confusion, memory problems, delirum, disorientation, inability to concentrate, dry mouth, constipation, blurred vision, increased body temperature, difficulty urinating, sexual dysfunction, worsening of glaucoma, sleeplessness, agitation, uncontrolled muscle movements, and tingling in the extremities. Again, some of these side effects are identical to the symptoms the depressed person is being treated for! You also have to be wary of "hypotensive effects" that is, sudden, drug induced drops in blood pressure that occur when you stand up suddenly. These can result in injuries, heart attacks or strokes. And because they can cause the heart to race, the drugs are especially dangerous for people with heart problems.
If at all possible, it's wise to look to every avenue before resorting to anti depressants. However, if you or relatives are convinced that you are one of the small core of people who would benefit from these drugs, the HRG suggests that you do the following:
* Have a electrocardiogram done and your blood pressure taken before you start on the drug.
* Begin the medication with a dose of one third to one half the usual adult dose (l5-25 mg) and increase very slowly.
* Make sure your doctor gives you a week's worth of pills at a time, so that you cannot use them to commit suicide.
* Wean yourself off the drugs slowly, over several months, once treatment has been successful.