What are antidepressants?
An antidepressants (also referred to as mood improver) is a drug that prevents the symptoms of depression.
Although scientists are still figuring out how antidepressants work, is a popular theory that severe depression the natural balance is restored between certain substances in the brains, creating a new chemical equilibrium and usually stabilize symptoms. This involves the so-called neurotransmitters, in particular, the substance serotonin. Patients are less gloomy and regain pleasure and interest in the things around him. By others (among others Irving Kirsch and Daniel Carlat) this explanation is disputed: they say that the fact that neurotransmitter levels are influenced by drugs does not mean that mental illness is caused by the same neurotransmitters. The funds usually works, but usually late improvement wait a while. In general, the medicine will operate only after two to four weeks.
Antidepressants can, especially by the target group itself, sometimes seen as a "medicine for the environment." Depressed behavior by the environment of the patient as a nuisance and annoying experience, through the use of antidepressants reduces this. If the depression is caused by an unpleasant or traumatic event (reactive depression), it is for the treatment of depression which is at least as important to tackle the cause whenever possible. To illustrate: a person who is a victim of systematic bullying may get out of severe depression. By use of antidepressants symptoms of his depression may indeed be fought, but it will not disappear bullying itself, with the result that the patient even after his treatment will continue to be the target of harassment.
Use of antidepressants
In the Netherlands, are increasingly prescribed antidepressants. In 2007, 937,000 people received a total of 6.7 million prescriptions for depression prescribed. The number of people using antidepressants since 1999, each year has grown by 6 percent.
Indications
An antidepressant (plural: antidepressants) is primarily used to reduce the symptoms of depression. In addition, this group of drugs can have a beneficial effect in anxiety disorders such as panic disorder, social phobia, and obsessive-compulsive disorder. Furthermore, antidepressants are used in the treatment of bulimia nervosa and PMDD (Premenstrual Dysphoric Disorder, a mood disorder related to the menstrual cycle).
Action
Antidepressants affect the transmission of impulses between nerve cells by neurotransmitters, also called the neurotransmission. Most antidepressants are neurotransmitters agonists that the availability of serotonin and / or noradrenaline increase in the brains. Over time occurs with depression often a significant improvement in: patients regain their enjoyment of life and interest in the environment increases. In general, the desired effect occurs only after two to four weeks.
It is not known how the anti-depressant effect is created. More recent research shows that the effect is also related to the decrease in the number of receptors or the expression of growth factors (in particular BDNF), whereby the neuron makes more connections with other neurons. It is also now known that depression is associated with an impaired stress response. An important role is played by the hormone corticotrophin releasing hormone (CRH).
Side effects of antidepressants
Initially, mainly effects that come to the fore. These depend on the agent selected and the individual sensitivity. Examples include: dry mouth, anxiety, gastrointestinal discomfort, anxiety and changes in sleep patterns. There also should be considered a temporary increase in suicidality because the person already deploys more initiative, but improvement in mood still waiting for it. Most side effects go away after a while or significantly reduced. However, they can also be a reason to stop prematurely with the drug: approximately 19% discontinue use within four weeks. Often short-term side effects are milder when the dose is slowly increased.
Side effects that may in the long run cause problems, weight gain and sexual dysfunction. The sexual dysfunction characterized by delay or absence of orgasm, decreased libido and erectile dysfunction. It is not uncommon to try two or three different agents before sufficient effect and tolerance can be achieved. Erectile problems can provide a drug as Viagra outcome (or related drugs).
From a large long-term study, the Women's Health Initiative in which 136,000 women were followed, showed that among the 5,500 women in this study who used an antidepressant appeared significantly more deaths and more strokes than among those who did not use antidepressants. It does not matter whether a selective serotonin reuptake inhibitor (SSRI) was used or a tricyclic antidepressant, in both cases there was about 2% per year extra risk.
Particulars
If the drug treatment should continue this strike for several months to prevent the symptoms from returning. In recurrent depression (depression that occur more than once) is recommended (much) longer using drugs. In many antidepressants that are used for more than three weeks, there withdrawal symptoms may occur if the medication is discontinued abruptly. In those cases, the dosage is slowly reduced. Also when switching to another antidepressant, it is usually necessary to reduce first of the current medications. Sometimes a longer "washout" period is necessary, in particular in MAOIs.
Groups
Antidepressants can be classified in different ways. Here is assumed: reuptake inhibitors, MAO-inhibitors, and a residual group.
Reuptake inhibitors
Reuptake inhibitors impede the normal functioning of the neurotransmitter transporter that pumps back to the neuron from which it is released. As a result, the concentration increases transmitter substance in the synaptic cleft increasing. The operation is related to the fact that the receptors of the postsynaptic neuron better "fed 'remain with the neurotransmitters. The cause of depression depends namely a (presumably) together with a deficiency of certain neurotransmitters in the brains. This means so sure that this deficit is eliminated.
Can be distinguished:
- TCA (tricyclic antidepressants) (so named because of their chemical structure) and related compounds, are older means almost all more or less inhibit the reuptake of serotonin and norepinephrine (eg, amitriptyline, imipramine, clomipramine). Compared with the more modern re-uptake inhibitors (see below), these agents have a relatively unfavorable side-effect profile, and they are not selective. Indeed, there is also affect muscarine, histamine and adrenergic receptors. In overdose, they are also dangerous (cardiotoxic). The advantage is, however, that there is a lot of experience has been gained with it in the course of the years. In addition, they are probably more effective than antidepressants which inhibit the reuptake of only one neurotransmitter.
- SSRI's (Selective Serotonin Reuptake Inhibitors) inhibit the reuptake of serotonin (eg, citalopram, fluoxetine, and paroxetine). SSRIs affect the plasma levels of other drugs by liver enzyme induction.
- NRI (Norepinephrine Reuptake Inhibitors) inhibit the reuptake of norepinephrine. Examples include reboxetine (Edronax® in Belgium) and nortriptyline (Nortrilen® in the Netherlands and Belgium) belonging to the TCAs, but nevertheless exhibits a very high selectivity noradrenergic.
- SNRI's (serotonin norepinephrine reuptake inhibitors) inhibit the reuptake of both serotonin and noradrenaline (e.g. venlafaxine in higher doses). Because SNRIs, as well as most TCAs, working on two neurotransmitters, they are also called "dual reuptake inhibitors" mentioned.
- NDRI (norepinephrine-dopamine reuptake inhibitors) inhibit the reuptake of norepinephrine and dopamine. The main representative is bupropion. This drug is also used to facilitate smoking cessation. As an antidepressant, the recently registered.
Monoamine oxidase inhibitors reduce the activity of the MAO enzyme. As a result, the breakdown of serotonin, norepinephrine and dopamine slowed down, thereby increasing the concentration of this transmitter substances rises. One distinguishes:
non-selective and irreversible inhibitors of mono-amineoxydase (e.g., tranylcypromine). This kind of drugs can have serious side effects. For example, there may be so-called 'cheese'-effect to occur, whereby tyramine (which, inter alia, in salami, banana, chocolate, certain types of old or soft cheese and present in red wine) in the complete inhibition of the MAO can no longer be broken down and this causes concentration in severe hypertension.
reversible MAO-A inhibitors (RIMA's) (eg moclobemide)
Other resources
- Nassa's "A noradrenergic specific serotonergic antidepressant" noradrenaline and serotonin availability increases, including by blocking the receptor for car noradrenaline (eg, mirtazapine).
- Agomelatine A new product that is authorized in the Netherlands recently. It is available under the brand name Valdoxan. The special is that it also affects the melatonin receptor (agonist).
- St. John's Wort (or Hypericum perforatum) is a natural preparation which efficacy has been demonstrated in depression. It is well tolerated and is available without prescription. That does not mean that St. John's Wort can not hurt. The effects of other medications (including oral contraceptives) can reduce it. It must not be combined with other antidepressants.
- S-adenosyl-methionine (SAMe) is an amino acid exhibiting an antidepressant effect in high doses, which is comparable to that of standard antidepressants. It works very quickly: if it catches on the antidepressant effect within a few days to a week noticeable. The side effects are headache, restlessness, insomnia, and diarrhea. The role of the agent in conventional medicine is still uncertain, partly because of the poor quality of the studies.
- Lithium (carbonate), and a salt of lithium carbonate. Used primarily in bipolar disorder.
In 2008 we will research a new group of agents: the "triple reuptake inhibitors" (perhaps later known as TRIS). They inhibit the reuptake of serotonin, norepinephrine and dopamine. One expects this means greater effectiveness and fewer side effects (especially sexual dysfunction). These funds are in 2008 still under investigation and therefore at that time not yet available. They have temporary names like PRC200-SS and JNJ 7,925,476.
Research on the relationship between stress and depression have produced a new group of agents: the CRH-1 receptor antagonists.
Only effective for severe depression
In January 2008, US researchers reported, Turner and colleagues, 12 the effectiveness of antidepressants was exaggerated, because studies with negative or questionable results were not published.
After a meta-analysis of 50 studies, on the basis of data which were supplied to the FDA, Kirsch and colleagues concluded that the new generation of antidepressants (fluoxetine, venlafaxine, nefazodone, and paroxetine) no significant clinical improvements yielded in patients with moderate-to- very severe depression. Only the most severely depressed patients showed significant clinical improvements. According to researchers, this can be attributed to a reduced sensitivity to the placebo effect of this group and not a greater sensitivity to the medication. Based on these results, the researchers concluded that there is little reason to prescribe these new generation antidepressants to depressed patients, except for the toughest cases, or when alternative treatments have proved ineffective.
Finally
Usually antidepressants are prescribed in combination with a form of psychotherapy. It happens that there is no or insufficient response to the first plea. In that case, it is switched to an antidepressant from a different group. If that does not, then there are often lithium is added. If still not received a satisfactory effect, is usually prescribed an irreversible MAOI. In some cases turns out that the depressive symptoms (enough) decrease. Typically, then switched to ECT (electroconvulsive therapy).
In addition to the prescription of antidepressants, attention should be paid to psychosocial factors, insofar as these play a causative role or entertaining. The treatment of depression, namely, can never be limited to only a biological approach.