Reboxetine and Depression

Depression is a huge problem. In the US alone depression strikes about 17 million American adults each year which is more than cancer, AIDS, or coronary heart disease (National Institute of Mental Health (NIMH)). According to the U.S. Department of Health and Human Services major depression affects 15 percent of Americans at some point during their lives. Unfortunately the effects of depression can be devastating and even simple every day things like eating, sleeping, or just getting out of bed can become almost impossible.

There are a myriad of treatments available for depression. However, Reboxetine, the first selective noradrenaline reuptake inhibitors (NARI), may be the drug that will provide you with the help that you are looking for. When depression occurs there may be a decreased amount of a chemical called noradrenaline released from nerve cells in the brain. A release of noradrenaline acts to lighten mood. So when noradrenaline becomes reabsorbed into the nerve cells, it no longer can affect mood.

Reboxetine works by preventing this re-absorption of noradrenaline back into the nerve cells. Therefore, it helps prolong the mood-lightening effect of any released noradrenaline, which helps relieve depression.

But before we look at Reboxetine in more detail, it helps to understand a little more about depression itself.

What causes Depression?

There are many reasons why someone can become clinically depressed and lots of theories about how depression occurs e.g. genetics, how the brain develops, stress etc. Indeed, depression in an individual may not just be a result of one particular cause but arise as a result of a combination of factors. What is known, however, is that in chronically depressed people low levels of serotonin and noradrenaline in the brain are chemical symptoms, if not necessarily causes, of their depression. Too little serotonin or noradrenaline can contribute to a person becoming depressed.

What are serotonin and noradrenaline?

Serotonin is a monoamine neurotransmitter. It is involved in the control of many things including mood, emotions, being asleep or awake, feeding and temperature regulation. If you have too little serotonin you will feel depressed and appear drowsy.

Noradrenaline (also referred to as norepinephrine) is a catecholamine which acts as both a hormone and a neurotransmitter and contributes to what is often referred to as the fight or flight response. This means that in times of stress, it helps prepare your body for physical activity by directly increasing your heart rate and blood pressure, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle. However, it is also implicated in the control of sleeping and wakefulness, arousal, mood, emotion and drive. Too little noradrenaline and you are likely to feel depressed, sedated, dizzy, and have low blood pressure.

The main difference between serotonin and noradrenaline in terms of depression is that whereas serotonin plays a vital role in anxiety and mood, noradrenaline is essential for maintaining drive, self-assertiveness and the capacity for reward.

The Treatment of Depression

During the 1980s and early 1990s the role of noradrenaline in the treatment of depression was somewhat neglected in favour of serotonin. This was mainly due to the advent of the selective serotonin reuptake inhibitors (SSRI’s) such as Prozac (fluxotine) and Zoloft (sertraline).

SSRI’s allow serotonin to be utilized more effectively in the brain without having any real direct influence over the levels of other neurotransmitters. Indeed, SSRIs are now the most widely prescribed anti-depressants in many countries.

However, by the close of the 20th century a new third generation of antidepressants had become available - selective noradrenaline reuptake inhibitors (NARIs) of which Reboxetine was at the vanguard of this development.

Indeed, it was the development of Reboxetine by Pharmacia (now Pfizer) as the first NARI that finally allowed clinical investigation of the role of the noradrenergic system into different aspects of depressive disorders. Such was the success of Reboxetine, by early 2007 it had been licensed for use in over 60 countries.

How does Reboxetine work?

Reboxetine increases the amount of noradrenaline in the brain. It acts by blocking the recycling (reuptake) of noradrenaline. This means that the next time a neuron sends an electrical impulse, there is more transmitter noradrenaline available, meaning a stronger message is passed, and activity in that part of the brain increased.

Studies into the use of Reboxetine

Clinical trials have shown that Reboxetine is an effective treatment for alleviating depression.

In short-term trials (4-8 weeks duration), researchers have demonstrated that Reboxetine is as effective as fluxotine in the treatment of major depression. Indeed, in a study of a group of severely depressed patients, Reboxetine was found to be significantly more effective than fluxotine.

In a longer term study (12 months duration), Reboxetine was shown to be superior to the placebo in the prevention of relapse and recurrence of depression. At the 12 month assessment, 78% of patients treated with Reboxetine were classified as in remission, compared with 45% of patients in the placebo group.

Furthermore, in a review of over 30 studies involving third generation NARIs, a team from the University of Melbourne, Australia concluded that they were at least as effective (in some cases more so) than SSRI’s and just as safe as SSRI’s.

Why should I take Reboxetine?

Primary Benefits

There are number of reasons why you would use Reboxetine as the drug therapy of choice:

• Where depression persists when SSRI’s have been unsuccessful
• Reboxetine may be more effective in treating symptoms brought on by deficiencies in noradrenaline such as impaired attention, problems concentrating, fatigue and memory deficits
• Reboxetine is as safe to take as an SSRI and therefore offers greater safety than older style tricyclic antidepressants or monoamine oxidase inhibitors
• Reboxetine does not increase agitation - core symptoms of depression, such as anxiety and agitation, can often be exacerbated by antidepressants.
• Studies have indicated that Reboxetine may be useful in the treatment of panic disorder, Parkinson’s Disease and bulimia
• Reboxetine is not addictive. However, if one has taken the drug for 8 weeks or more some mild "discontinuation" effects may be experienced if its use is withdrawn abruptly (although this is very, very rare with Reboxetine)

Reboxetine and Improvements in Social Behaviour

Reboxetine is thought to improve social behaviour because noradrenaline is associated with increased social engagement and co-operation and a reduction in self focus. Whilst this theory has not yet been rigorously tested, in a study carried out by researchers from King’s College, London, 60 healthy volunteers were randomly assigned either a single 4mg dose of Reboxetine, a placebo or a dose of Citalopram (an SSRI). On observing the effects, the researchers noted that during the playing of a game, more of the volunteers on Reboxetine were co-operative players. They concluded that Reboxetine had clear effects on social behaviour.

Reboxetine and the Elderly

Depression is unfortunately for many an all too common symptom of getting old. Although there is a wide range of anti-depressant therapy on offer, elderly patients are particularly susceptible to the potential side-effects of many anti-depressants because of age-related physiological changes. In a pilot study carried out by a team from Soave, Italy, 12 elderly female patients (75-87 years) suffering from either major depression or dysthymia received Reboxetine over a 4 week period. At the end of the study period 7 of the patients were clinically assessed to be "much" to "very much" improved with the Reboxetine being tolerated well by the majority of the patients.

Dosage

The recommended starting dose is 4mg twice daily, increasing to 10mg daily if necessary after 3 weeks.

Elderly persons should start at a dose of 2mg twice daily, increased to a maximum of 6mg daily if necessary after 3 weeks.

Reboxetine tablets should be swallowed with at least half a glass of water whilst sitting or standing. Although it is not necessary to take them with food, it is a good idea to take them at the same time each day and taking them at mealtimes may help you adhere to this.

It may take as long as 2 weeks or more before Reboxetine starts to have any effect on your mood, and a further 3 or 4 weeks for this effect to be reaching its maximum. Unfortunately in some people the effect may take even longer to occur (potentially several months).

Side Effects

The most common side effects experienced are:-

• Dry Mouth
• Constipation
• Drowsiness – if this does occur it can last for a few hours after taking your last dose
• Dizziness
• Sweating – particularly at night
• Insomnia

More uncommon side effects are:-

• Palpitations – when your heart beats faster
• Postural Hypotension – low blood pressure that causes you to feel dizzy when you stand up
• Urinary Retention – an inability to pass much urine

In very rare circumstances, Reboxetine can cause sexual dysfunction, with a loss of libido and/or an inability to achieve orgasm.

Caution

• The use of Reboxetine in conjunction with monoamine oxidase inhibitors (MAOI’s) is not recommended
• Patients with narrow angle glaucoma should also avoid Reboxetine
• The possibility for a switch to mania/hypomania exists, especially in patients with bipolar disorder
• Reboxetine should be used with caution in men with prostatic enlargement, and with caution in all patients with a history of epilepsy

Information regarding exposure to Reboxetine during pregnancy and whilst breast feeding is limited. Therefore its use is not recommended.