What are Zoloft and Risperdal used for?
Antidepressants: Sertraline opens up new therapeutic options
At least 5.5 million (8 percent) of all Germans under 65 years of age are depressed, and this number increases disproportionately with age. Despite the high incidence, there are still many false and trivializing ideas about the causes and course of depression in the population today, so that a third of those affected do not see a doctor. But even those patients who seek medical treatment do not always receive the optimal therapy.
Often no optimal therapy
One study showed that only four percent of all patients in Germany are treated with the best drugs according to current knowledge. Another eight percent receive older antidepressants, 23 percent tranquilizers or phytopharmaceuticals. A third of the patients receive psychological care only.
In addition to the high level of suffering for those affected, depressive illnesses also cause great economic damage. Since depression often manifests itself in somatic complaints and depressed patients suffer more often and for longer from organic diseases, there are two to three times more days off work. The high number of suicides that can be traced back to depression is particularly frightening. Better patient education and the adaptation of medical treatment to the latest state of knowledge are urgently needed.
Tricyclic antidepressants: lack of receptor selectivity
Tricyclic antidepressants, MAOIs, and the newer selective serotonin reuptake inhibitors are used to treat depression. A disadvantage of tricyclic antidepressants is their lack of receptor selectivity. In addition to the desired inhibition of noradrenaline (NA) and serotonin (5-HT) reuptake, muscarinic acetylcholine (ACH) and histamine receptors (H) are also blocked in therapeutic doses, which is responsible for numerous undesirable effects such as dry mouth, constipation and sleep disorders is. The blockade of alpha1 adrenergic receptors leads to hypotonic circulatory disorders. The membrane-stabilizing effect of the tricyclic antidepressants on the heart is particularly fatal, because even small overdoses can have a cardiotoxic effect and trigger arrhythmias. The therapeutic range of these substances is therefore narrow and their use in multimorbid patients is severely limited.
SSRI: better tolerated due to selective effect
Selective serotonin reuptake inhibitors (SSRI) such as fluoxetine, paroxetine, fluvoxamine and citalopram, on the other hand, have a selective inhibitory effect on 5-HT reuptake in therapeutic doses. Effects on other receptors only occur in higher doses, with the individual substances differing in their selectivity.
Three years ago a new representative of this substance class was introduced in Germany with sertraline, a dichlorophenylnaphthylamine. Comparative studies show that of all SSRIs, sertraline has the highest affinity for the 5-HT receptor. It works there 36 times stronger than fluoxetine. Only in a 100-fold overdose does sertraline show side effects by blocking acetylcholine, noradrenaline or alpha1 receptors.
High therapeutic breadth
Sertraline has a very wide therapeutic range - even in a 160-fold overdose, no toxic effects were found. The most common side effects of 5-HT receptor blockage in the gastrointestinal tract are nausea and diarrhea. The symptoms are usually mild and decrease as the therapy continues through down-regulation of the receptors. Other undesirable effects can include headaches and ejaculation delays. An epileptogenic effect as with fluoxetine was not found.
With all SSRIs, simultaneous administration with MAO inhibitors leads to serious side effects; there have also been reports of deaths. An interval of at least two weeks must be strictly observed here. Concomitant use of sumatriptan should be avoided or carefully monitored during sertraline therapy.
No accumulation to fear
In contrast to its predecessor substances, sertraline does not inhibit its own metabolism. In the clinically relevant dose range of 50 to 200 mg per day, it shows linear pharmacokinetics, so that an accumulation as with fluoxetine is not to be feared. The change in pharmacokinetics observed with all other SSRIs in patients over 65 years of age does not occur with sertraline. Its terminal half-life of 25 hours enables it to be administered once a day. The renal elimination of sertraline is so low that a dose adjustment is not necessary in patients with renal insufficiency.
Sertraline is hepatically metabolized to the clinically inactive desmethylsertraline. As the only representative of its class of substances, sertraline does not inhibit the cytochrome P450-2D6 isoenzyme, which is important for the breakdown of many drugs. Sertraline thus offers greater safety in comedication.
Sertraline opens up new therapeutic options
The antidepressant therapy of elderly and multimorbid patients poses a major problem. On average, patients at the age of 60 take five medications a day; at 75, the number increases to seven. The interactions to be feared, especially with the tricyclic antidepressants, have hitherto prevented adequate treatment of age-related depression. With an estimated 25 percent of depressed people in old people's homes and the proven coincidence of depression with Alzheimer's disease, the urgent need for action becomes clear. With its potency comparable to tricyclic antidepressants, the more favorable side effect profile and the reduced interactions with other drugs, sertraline opens up new therapeutic options. There are first indications that sertraline could have a positive effect on vigilance in Alzheimer's patients.
Some findings suggest that sertraline has an affinity for dopamine and sigma1 receptors, which may explain its good effect compared to other SSRIs in severe depression of the melancholic type with psychomotor inhibition and in delusional depression.
Faster onset of action and fewer treatment discontinuations
In several studies that compared sertraline with tricyclic antidepressants and the SSRIs with one another, sertraline showed a faster onset of action and fewer treatment discontinuations due to side effects. Its better compliance ensures the necessary treatment duration of at least nine months for depression and enables recurrence prevention over several years.
Unlike other SSRIs, sertraline does not cause weight loss or agitation. Weight gain and psychomotor inhibition as under treatment with tricyclic antidepressants are also not to be feared. Its anxiolytic active component makes it possible to use sertraline in the treatment of depression with anxiety and delusions and to save sedative drugs.
Approval for the treatment of post-traumatic stress disorder
Based on new study results, sertraline was the first SSRI to be approved in the USA for the treatment of post-traumatic stress disorder. This disease made headlines after American soldiers returned from war zones. It is estimated that after accidents, natural disasters or violent attacks, ten to twenty percent of those affected develop post-traumatic stress disorder, with women being more frequently affected.
Since sertraline has no influence on the breakdown of alcohol, its use in alcoholics is possible. Another possible use for sertraline is in the treatment of depression after a heart attack.
Depression and heart attack
Several studies show a link between the occurrence of depression and heart disease. The increased cardiovascular morbidity and mortality are particularly noticeable when depression occurs after an acute heart attack. Studies have shown that half a year after the infarction, almost four times as many of the patients classified as depressed had died compared to the non-depressed patients. It is not yet known how depression affects prognosis, but it is clear that it should be viewed as a risk factor for heart disease and sudden cardiac death. To date, there is no adequate antidepressant treatment of post-infarct patients, since potential cardiovascular side effects of the antidepressants represent an additional risk. An antidepressant that does not adversely affect cardiological parameters could fill a therapeutic gap here.
A pilot study with 26 patients showed that sertraline has no effects on the ECG and counteracts the formation of thrombus. The study shows a significant improvement in depressive symptoms. Statistically relevant results on a reduction in mortality with sertraline could not be provided due to the low number of patients and a lack of placebo comparison.
As part of the ongoing international, multicenter follow-up study SADHART (Sertraline Antidepressant Heart Attack Recovery Trial), sertraline is being tested against placebo in 330 patients with a heart attack. Initial results suggest that sertraline could be useful in the treatment of these high-risk patients.
Effective treatment costs count
Despite the obvious advantages of selective serotonin reuptake inhibitors in depression therapy, their prescription numbers in Germany are still relatively low. One of the main reasons is likely to be found in the higher price of these preparations. In the USA, the SSRIs have almost completely replaced other antidepressants. Due to the differently structured insurance system, the focus here is on the total effective treatment costs, which can be reduced in the long term with the best antidepressant therapy.
Sources: Prof. Dr. S. H. Preskorn, MD, Wichita, Kansas, USA, press conference "3 years of sertraline (Zoloft)", Dresden, September 15, 2000, hosted by Pfizer, Karlsruhe. Shapiro, P. A., et al .: Open pilot study on sertraline for the treatment of major depression after acute myocardial infarction (SADHART study). At the. Heart J. 37: 1100-1106 (2000). Kötter, H. U., et al .: Sertraline - a modern, selective serotonin reuptake inhibitor in the antidepressive therapy of multimorbid patients. Drug Therapy 17, 395-402 (1999).
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