Tag: antidepressants

The problem with industry-funded drug trials

How much can we trust the results of clinical trials, especially ones that have been funded by companies with vested interests? This is the question we should continually ask ourselves, after the debacle of Seroxat.

The active ingredient of Seroxat is paroxetine. Medicines are known by two names, one of the active ingredient, the one that gives it the scientific name, and the other, the brand name. For example, the ingredient paracetamol is marketed under Neurofen, among other names. Companies that manufacture their own brand of medicine may decide to market it little more than their company name before the active ingredient, for example, Tesco paracetamol or Boots Ibuprofen, in order to distinguish it from other rival brands and aligning it with an already recognised scientific name, but without the associated costs of having to launch a new product brand.

Paroxetine is an anti-depressant and made its name as one of the few anti-depressants to be prescribed to children. However it was withdrawn from use after re-examination of the original scientific evidence found that the results published in the original research were misleading and had been misconstrued.

The prescription of medications to children is done under caution and monitoring, as there are various risks involved. Firstly, there is the danger that their bodies adapt to the medication and become resistant, thereby necessitating either higher doses in adult life, or a move on to stronger medication. In this instance there is the possibility that rather than addressing the problem, the medication only becomes a source of life-long addiction to medication. The second risk is that all medicines have side effects and can cause irreparable damage to the body in other regions. For example, the use of aspirin in the elderly was found to damage the lining of the stomach.

Equally worrying is the effect of these drugs on the health of the mind. Some drugs, particular those for mental health, are taken for their calming effect on the mind. The two main types of mental health drugs can be said to be anti-depressants and mood stabilisers, and while the aim of these drugs is to limit the brain’s overactivity, some have been found to trigger suicidal thoughts in users instead, ironically performing the function they were meant to discourage.

Children are often currently either prescribed adult medication in smaller doses of half strength instead, but the difficulty in assessing the dosage is that it does not lend itself to being analysed on a straight line graph. Should children under a certain age, say twelve for example, be prescribed as doseage based on age? Or if the most important factor in frequency is the body’s ability for absorption, should we prescribe based on other factors such as body mass index?

So when Seroxat came on to the market marketed as an anti-depressant for children you could almost feel the relief of the parents of the young sufferers. A medical product, backed by science and research, suitable for children, approved by the health authorities. Finally a medical product young sufferers could take without too much worry, and one – having been tested with young children – that parents could be led to surmise would be effective in managing their children’s mental health.

Except that Paroxetine, marketed as Seroxat, was not what it claimed to be. It has been withdrawn from use after scientists found, upon re-analysing the original data, that the harmful effects, particularly on young people were under-reported. Furthermore, researchers claim important details that could have affected the approval of its license were not made public, because it might have meant years of research might have gone down the drain.

When a medical product is launched, it is covered under a twenty-year no-compete patent, which means that it has a monopoly on that medicine for that period. While one might question why that is so, it is to protect the time spent by the pharmaceutical companies in investing in research and marketing the product, and give it a time period to establish a sizeable market share as a reward for developing the medication.

Twenty years for a patent might seem like a long term, but as companies apply for it while the product is in the early stages of development, in order that its research is not hijacked by a competing pharmaceutical company, they are often left with a period of ten years or less by the time the medical product has some semblance of its final form. The patent company has that amount of time to apply for a license and to market and sell the medication. After the original twenty years has elapsed, other companies can enter the fray and develop their own brands of the medicine. They, of course, would not need to spend the money on research as much of the research will have already been done, published, and accessible – enough to be reverse-engineered in a shorter space of time. Pharmaceutical companies are hence always engaged in a race against time, and if a product hits a snag in trials, mass production is put on hold – and if the company is left with anything less than five years to market its product, it is usually not long enough a period to recoup research costs. And if it is less with anything less than three years, it might as well have done the research for the companies that follow, because it will not recover the costs of research and marketing. While not proven, it is believed that pharmaceutical companies hence rush out products which have not been sufficiently tested, by emphasising the positive trial results, and wait for corrective feedback from the market before re-issuing a second version. It is not unlike computer applications nowadays which launch in a beta form, relying on user feedback for improvement, before relaunching in an upgraded form. The difference is software has no immediate implications on human health. Medication does.

Researchers who re-examined data from the medical trial of the antidepressant paroxetine, found reports of suicide attempts that had not been included in the original research paper. And because the makers of paroxetine, GlaxoSmithKline (GSK), had marketed paroxetine as a safe and also effective antidepressant for children, even though evidence was to the contrary, GSK had to pay damages for a record $3 billion for making false claims.

In the original research trials, GSK claimed that paroxetine was an effective medication for treating adolescents with depression and it was generally well-tolerated by the body with no side effects. Subsequent analysis found little advantage from paroxetine and an increase in harm in its use, compared to placebo.

The whole issues highlights the difficulty in trusting medical trials whose data is not independently accessed and reviewed.

The current stance on data is that pharmaceutical companies can select that clinical data they choose to release. Why is this so? We have already covered the reason for this. They have committed funds to research and are hence protective (and have right to be) protective of the raw data generated, particularly when competitors are waiting in the fold to launch products using the same data.

If you were a recording artist, and hired a recording studio for two weeks, musicians to play for you and sound engineers to record your work, at the end of the two weeks, you might have come up with a vast amount of recordings which will undergo editing, and from which your album will be created, then whatever has been recorded in the studio is yours, and you have the right to be protective about it in order that someone else might not release music using your ideas or similar to yours.

The problem is that when the pharmaceutical company initiating and funding the research is the one that will eventually market it first, and the clock is ticking against it, then it has a vested interest in the success of the product and is inherently biased to find positive outcomes that are advantageous to the product it creates.

Who would commit twenty years of time, research, marketing and finance to see a product fail?

The pharmaceutical company is also pressured to find these outcomes quickly and hence even the scientific tests may be already geared to ones that lead to pre-determined conclusions rather than ones that open it up to further analysis and cross-examination, and take up precious time or cause delay.

This creates a situation where only favourable data has been sought in the trials and only such data is made publicly available, leading to quick acceptance of the drug, a quick acquisition of a license and subsequently less delay heading into the marketing process.

The alternative is for independent review of the raw data, but this causes additional stresses on the time factor, and the security of the raw data cannot be guaranteed.

Despite the limitations of the current system, there are attempts to reform the system. The AllTrials campaign is a pressure group seeking independent scrutiny of medical data and has backing by medical organisations. The AllTrials group argue that all clinical trial data should be made available for the purpose of independent scrutiny in order to avoid similar issues to the misprescribing of paroxetine from repeated occurrence in the future.

The original study by GSK reported that in clinical trials 275 young people aged 12 to 18 with major depression were randomly allocated to either paroxetine, an older antidepressant drug called imipramine, or a placebo for eight weeks.

The researchers who reviewed the previous original study in 2001 found that it seriously under-reported cases of suicidal or self-harming behaviour, and that several hundreds of pages of data were missing without clear reason. It is likely these did not look upon paroxetine favourably.

Data was also misconstrued. For example, the 2001 paper reported 265 adverse events for people taking paroxetine, while the clinical study report showed 338.

The data involved examining 77,000 pages of data made available by GSK, which in hindsight, might have been 77,000 pages of unreliable data.

This study stands as a warning about how supposedly neutral scientific research papers may mislead readers by misrepresentation. The 2001 papers by GSK appear to have picked outcome measures to suit their results.

It subsequently come to light that the first draft paper was not actually written by the 22 academics named on the paper, but by a ghostwriter paid by GSK.

That fine for GSK might be seen as small in light of this. Certainly the reliability of industry-funded clinical trials, and how the process can be overhauled, is one we need to be considering for the future.

Mental Health Medication – Concerns and Ethics

One of the most common questions about mental health problems is whether people need medication to deal with them, or whether they can be simply dealt with through therapy. Mental health problems can range from the not so severe – such as mild anxiety – to more severe problems like long-term depression. There are some that see medication as a short term, quick fix solution – it will give relief fast, but it doesn’t really teach one to deal with the heart of the problem – hence the suggestion of therapy and counselling. Yet there are those that remain convinced that while therapy re-educates the patient and deals with mental health difficulties on a long term basis, sometimes medication provides a greater level of immediacy in providing a solution, that its role cannot be denied. Should I take medication for _______” is one of the most frequent queries received. The ideal solution is probably a combination of medication and therapy, whilst gradually reducing the level of medication and therapy as the patient progresses.

Medication can be useful. For example, for those with paralysing anxiety, medication can minimise the stress and anxiety placed upon an individual by these stressors until the level of anxiety is at a comfortable and manageable level, enabling one to live their daily life while keeping their anxiety at a level they can control. However, for individuals with a severe mental health condition such as schizophrenia, the use of medication may be necessary in order to attain a level of mental stability and hence safety.

But medication is not just for a stabilising calm influence. For those, however, for whom facing the day is a burden, and who remain unable to get out of bed in the morning because depression has stolen all motivation, mental health medication can provide a jumpstart, an impetus to face the day. Certain people may benefit from taking psychotropic medication. For example, a study funded by the National Institute of Mental Health found that some individuals who were prescribed the selective serotonin reuptake inhibitor (SSRI) Paxil, because they experienced moderate to severe depression, experienced positive changes in mood, together with significant improvements in depressive symptoms. There was a marked decrease in the level of neuroticism and a similar increase in extroversion. These effects occured over a period of eight weeks and were nearly equivalent to the changes most adults experience in the course of a lifetime.

According to Maslow’s hierarchy of needs, human beings must satisfy more basic needs such as food and shelter before they attend to more self-actualising needs. It is difficult for most people to focus on avenues of self-growth when they are in crisis or struggling with anxiety, depression, or other mental health conditions. In some cases the polarisation can even lead them further into depression. In this instance, medication can support the psychotherapy process, and a stabilised person can progress further in psychotherapy having had the needs at the lower end of the hierarchy addressed. For example, a study published in the Journal of the American Medical Association shows that cognitive behavioural therapy combined with targeted medication tends to lead to significant improvement of attention deficit hyperactivity symptoms in adults. And in the long term, of course, a common outcome of successful psychotherapy is the reduction or elimination of the need for medications, so medication can be viewed as a temporary measure.

And while we have to recognise its benefits for the short term, we have to realise that medication can be harmful for some individuals if taken over a prolonged period. Most, if not all, drugs come with potential risks and side effects. Some can be minimal and tolerable while others carry disadvantages best considered as trade-offs. The side effects range from physical ones to emotional and psychological ones. Physical side effects range from dizziness, drowsiness, or changes in appetite, and/or weight gain. Emotional and psychological side effects may range from mood swings, disinterest in activities, or emotional numbness and a lack of empathy. Prescribed over a long term, antipsychotics may cause permanent damage by leading to conditions such as tardive dyskinesia or Parkinsonism, and may even cause death. The death may not be triggered by physical caused, but by mental irrational thinking. A 2005 article in the Harvard Mental Health Letter spelt out in detail the increasing awareness of risks associated with SSRI antidepressants, such as a potential increase in suicidal thinking and behaviours for adults and children under 24 years of age. One could, however, speculate if the suicidal thoughts were triggered by the medication directly, or whether it was the prospect of lifetime medication without an apparent cure that caused these feelings of hopelessness. Whichever you look at it, it is fair to say that there are people who will benefit from taking these medications, but also people who may experience lasting harm as a result of antidepressant use. The use of medication remains a double-edged sword.

But there are lines of thought that ascribe that medication is not always a necessary process. While medication may be effective for treating certain conditions, researchers at the University of Pennsylvania and Vanderbilt University suggested that, over a period of 16 months, cognitive therapy was a more effective means of preventing a relapse into depression than antidepressants alone. Research findings published in the Journal of the Amercan Medical Association found that while antidepressants were helpful for those experiencing severe depression, milder to moderate forms of depression derived more benefit from other treatment options, such as therapy. A 2010 article published in Newsweek arrived at the same conclusions, suggesting that, for some individuals, antidepressants are little more than a placebo.

To summarise what I’ve said so far: mental health is best addressed through a combination of therapy and medication. Severe forms of mental depression, which require more immediate intervention, would benefit from prescription drugs and therapy, while therapy alone may be sufficient enough for milder forms. Medication provides short-term benefit, especially in higher forms of depression, but we must be cautious over its long-term use because it can have side effects.

Medication can interfere with the emotions as well as the psychotherapy process. One of the most common side effects of psychotropic medication is difficulty feeling certain emotions, perhaps even a lack of empathy, once enough doseage of a drug accumulates in a person’s system. When we consume too much of a drug that is meant to limit our nerves, for example, many people complain of losing the feelings they used to have, report a reduction in their ability to laugh or cry, or experience a decrease in libido. These are the effects of medicines with a calming influence. Other side effects extend to one’s sexuality and love relationships, such as diminished sexual interest. Medication can also limit hyperactivity in the brain, acting as an emotional relaxant, but this slows emotional processing for some, and in doing so, covering up underlying issues and causing the psychotherapy process to be slowed down. A possible consequence of taking too much medication and becoming numb to feelings is the increased likelihood that a person will not become conscious of the emotional or somatic burdens which can cause of stress and suicidal feelings. It may be stretching things a little, but if you view medication as a substance, just like we view alcohol – too much consumption leads to physical health problems, as well as a capacity for clear thought processing – we can get a better idea of how the prescription of medication might not always be a clear-cut issue.

Proponents of a little- or no-medication approach to mental health point out that many emotional and mental health issues are not reducible to a biochemical imbalance. Life events — what happens to and around us – can impact on our mental health, and because medications do not change how people relate psychologically to their experiences, medication alone cannot “fix” all psychological issues. In fact, the temporal masking of life circumstances by medication is probably what induces people to overdose in the first place, taking more medication to completely obviate one to one’s surroundings. Treatment with medication alone can be like stitching up a bullet wound without taking the bullet out first – dealing with the effects without dealing with the cause. It is one of the main criticisms of the medical profession.

Furthermore, an over-simplification of what causes depression has led to the development of anti-depressant drugs that are actually designed to treat or minimise stress. These medications are often of little use because they have been tested on animals, and for the laboratory animals such as rats chronic stress does not cause depression. Psychotherapy, on the other hand, is often able to discover and treat some of the mental health issues that may contribute to depression, such as psychological trauma and anxiety. For example, a 1995 Consumer Reports study shows that some individuals experiencing mental health issues were significantly helped by psychotherapy. The study found that long-term therapy had, in general, the most beneficial effect, and that treatment with therapy alone was no less effective than treatment with medication and psychotherapy.

In an article “Mind over Meds,” which appeared in a 2010 issue of The New York Times Magazine, Dr. Daniel Carlat, a psychopharmacologist, found that the individuals he treated responded better to a combination of treatment with psychotherapy and medication together than they did purely with medication alone. The provision of counselling in addition to medication helped them to be better able to understand the true nature of their concerns. His findings are supported by research that therapy can stimulate the growth of neurons and synaptic connections between neurons. However, medication for depression, anxiety, and other emotional problems do not stimulate the brain; instead they dampen the brain’s mental activity. Therapy is capable of healing core problems and facilitating long-term changes, and why medication alone cannot. But medication is important in areas where the mental thoughts of the individual needs to be reduced to a lower level of activity.

Psychotropic drugs are prescribed to treat a variety of mental health issues when those issues cause significant impairment to healthy functioning. They work by changing or balancing the amount of important chemicals in the brain called neurotransmitters. The reduction or increase of neurotransmitters such as dopamine, serotonin, and norepinephrine have shown better mood improvements in some individuals. The ideal s to achieve a tolerable balance of these chemicals in order for the individual to attain a healthy life. Psychotropic drugs are usually prescribed by a psychiatrist, a psychiatric nurse practitioner (PMHNP), or a primary care physician

According to the WHO, one in four individuals will experience a mental health issue at some point in their lives. Depression and anxiety are among the most common issues, and these issues can affect people regardless of age, gender, ethnicity, or background. Researchers cannot point to the triggers of mental health impairment, but they can be attributable to environmental factors, genetics, traumatic events or serious injuries and result in psychological symptoms that persist for years.

As we have seen before, for some individuals psychotropic drugs are often not enough are best used as a supplement, and not a replacement, to therapy. Social support from family and friends, structured therapy, lifestyle changes – all leading to a change of environment – can all be important factors in the recovery process. But in some severe mental health issues may require inpatient rehabilitation before the person experiencing them can return to everyday life.

Certain individuals who are prescribed psychiatric medications may prefer not to take them, or they find that these medications do not improve their symptoms enough to outweigh any side effects or risks. Before you take any medication, it is always advisable to speak with your GP or seek specialist advice.

One major cause of concern regarding mental health and medication is the practice of prescribing medications that were originally developed for adults to children. The increase in diagnoses of psychiatric conditions in children – bipolar in particular – has led to an increase in the amount of children who take psychiatric medications. Many of which have only been fully tested in adults, and children take them in smaller doses, but the long-term impact of medication, as well as the effect on children who have yet to reach puberty needs to be examined.

Several different types of medications are used to treat mental health conditions. These include antipsychotics and anti-depressants.

Antipsychotics: These medications are most often prescribed for the treatment of psychotic issues such as schizophrenia. These drugs fall into two categories, typical and atypical antipsychotics.

The brand name is listed first, and the active ingredient is in parentheses.

Typical antipsychotics include:
Thorazine (chlorpromazine)
Trilafon (perphenazine)
Stelazine (trifluoperazine)
Serentil (mesoridazine)
Prolixin (fluphenazine)
Navane (thiothixene)
Moban (molindone)
Mellaril (thioridazine)
Loxitane (loxapine)
Haldol (haloperidol)

Atypical antipsychotics include:
Abilify (aripiprazole)
Clozaril (clozapine)
Geodon (ziprasidone)
Risperdal (risperidone)
Seroquel (quetiapine)
Zyprexa (olanzapine)

Antidepressants are a broad category of psychotropic drugs used for treating depression. There are several different classifications of antidepressants:

Selective serotonin reuptake inhibitors (SSRIs): These medications gradually increase the amount of serotonin, a neurotransmitter, in the brain. Common SSRIs include:

Celexa (citalopram)
Lexapro (escitalopram)
Luvox (fluvoxamine)
Paxil (paroxetine)
Prozac (fluoxetine)
Zoloft (sertraline)

Monoamine oxidase inhibitors (MAOIs): A less common variety of antidepressant drugs, MAOIs are often a last option with complex, treatment-resistant depression. Common MAOIs include:

Emsam (selegiline)
Marplan (isocarboxazid)
Nardil (phenelzine)
Parnate (tranylcypromine)

Tricyclics (TCAs): These older antidepressant medications have been pushed to the sidelines by newer, generally safer medications. Still, some people do not respond to the new antidepressants, so TCAs may be prescribed. Tricyclic medications include:

Anafranil (clomipramine)
Asendin (amoxapine)
Elavil (amitriptyline)
Norpramin (desipramine)
Pamelor (nortriptyline)
Sinequan (doxepin)
Surmontil (trimipramine)
Tofranil (imipramine)
Vivactil (protiptyline)

Selective norepinephrine reuptake inhibitors (SNRIs): These medications work by slowly increasing the amount of norepinephrine in the brain. Common SNRIs include:

Pristiq (desvenlafaxine)
Effexor (venlafaxine)
Cymbalta (duloxetine)

Antianxiety/antipanic medications: These medications are used to treat a variety of chronic and acute anxiety issues, from generalized anxiety to panic attacks. Antianxiety and antipanic medications on the market include:

Ativan (lorazepam)
BuSpar (buspirone)
Inderal (propranolol)
Klonopin (clonazepam)
Librium (chlordiazepoxide)
Serax (oxazepam)
Tenormin (atenolol)
Tranxene (clorazepate)
Valium (diazepam)
Xanax (alprazolam)

Stimulants: Typically, stimulants are prescribed to people with attention-deficit hyperactivity (ADHD). They help regulate disorganized thought processes. Psychomotor stimulants include:

Adderall (amphetamine and dextroamphetamine)
Dexedrine (dextroamphetamine)
Ritalin (methylphenidate)

Mood stabilisers: This category of psychotropic medication is typically used to treat intense, repeated shifts in a person’s mood, which may be common for those experiencing bipolar, schizophrenia, or borderline personality. Many mood stabiliser drugs are also commonly categorized as anticonvulsant medications.

Lamictal (lamotrigine)
Lithium

In 2013, the most prescribed psychotropic drugs in the United States (with the number of prescriptions written during the year) were:

Xanax (alprazolam), 48.5 million
Zoloft (sertraline), 41.4 million
Celexa (citalopram), 39.4 million
Prozac (fluoxetine), 28.3 million
Ativan (lorazepam), 27.9 million
Desyrel (trazodone HCL), 26.2 million
Lexapro (escitalopram), 24.9 million
Cymbalta (duloxetine), 18.6 million
Wellbutrin XL (bupropion HCL XL), 16.1 million
Effexor XR (venlafaxine HCL ER), 15.8 million

Should one be dismayed by the number of prescriptions in a YEAR alone, as well as the various types of medications available? However you feel about them, they all point to mental health as a significant issue, one that we cannot ignore. We have, however, to cautiously consider that medications that seem appropriate at this time may not be at a later stage. Ultimately, it is best that we learn to function without additive medication in the long term, not just because of their side effects – but if we are being cynical, under pressures of financial cost, medical research may in time suggest that certain forms of mental health medication were inadequate in the first place, and if funding is withdrawn patients may find themselves dependent on medication that they have to make their own provisions for – or worryingly, do without.

And it would be unfortunately ironic if the concerns over provision for mental health became another life stressor.