SNRI

introduction

The so-called serotonin norepinephrine reuptake inhibitors (SNRI) are drugs used primarily in the treatment of depression. The most important active ingredients in this class of drugs are venlafaxine and duloxetine. The name refers to the property of these drugs to exert their effect on both the serotonin level and the norepinephrine level in the central nervous system. This property distinguishes the serotonin noradrenaline reuptake inhibitors from other antidepressants that only act on one of the two substances.

„Reuptake"Describes the re-uptake of messenger substances, in this case noradrenaline or serotonin, into the nerve cells, while the term"Inhibitor“Represents a technical term for an inhibitor. In summary, serotonin-noradrenaline reuptake inhibitors are inhibitors of the reuptake of serotonin and noradrenaline into the nerve cells.

The drugs available

The active substance Venlafaxine is available under the following trade names:

• Efexor®, Trevilor® retard, venlafaxine generics

The active ingredient duloxetine under the trade names:

• Ariclaim, Cymbalta®, Duloxalta®, Xeristar®, Yentreve®, Duloxetine generics

Milnacipran at:

• Milna-neurax®, Ixel, as well as numerous trade names abroad: Salvella®, Toledomin, Joncia, Tivanyl®, Dalcipran

Indication and field of application of SNRI

Serotonin norepinephrine reuptake inhibitors such as venlafaxine or duloxetine can be used to treat depression, both in acute and long-term therapy. In addition to the serotonin-noradrenaline reuptake inhibitors, there are also selective serotonin reuptake inhibitors and selective noradrenaline reuptake inhibitors for the treatment of depression. Which of the drugs is used depends on the severity of the depression in the affected patient.

A deficiency in serotonin in certain areas of the brain is primarily responsible for the depressed mood and joylessness of the patient. On the other hand, a norepinephrine deficiency is said to cause listlessness and poor concentration. Depending on which of the symptoms predominate in the patient, you will either choose an inhibitor of serotonin reuptake or one of norepinephrine reuptake or a mixed inhibitor that inhibits the reuptake of both substances. However, these assignments are more of a basic decision-making aid than a definitive "Black and white criteria" to understand.

The described drive-increasing effect of the selective noradrenaline reuptake inhibitors also has disadvantages. Especially in severely depressed patients, their use, as the drive is increased significantly more than the mood, can under certain circumstances provoke self-endangering actions up to suicide. Because of this risk, selective norepinephrine reuptake inhibitors are only rarely used to treat depression, for example in patients with severe drive disorders and an unrestricted mood.

In addition to their use in the treatment of depression, serotonin-norepinephrine reuptake inhibitors are also used in patients with social phobia or those with obsessive-compulsive disorder.

Find out more about the topic here: The role of serotonin / neurotransmitters in depression.

Effect of SNRI

As already described above and evident from the name, serotonin-noradrenaline reuptake inhibitors (SNRI) inhibit the reuptake of serotonin and noradrenaline into the nerve cells. To understand this mechanism, one should consider the structure of a synapse, i.e. a connection point between two nerve cells.

A synapse consists of the presynaptic End of a nerve cell and that postsynaptic End of another nerve cell. In order to transmit certain information, the first nerve cell releases messenger substances (Transmitter) in the gap between the two nerve cells. These move towards the cell membrane of the second nerve cell, are absorbed into it and can there transmit the information in various ways.

Synapses in which serotonin or noradrenaline take on the role of the transmitter are therefore preferably controlled by the serotonin-noradrenaline reuptake inhibitors. The SNRIs inhibit the transporters that push some of the serotonin or noradrenaline molecules released from the first nerve cell back into the first nerve cell - these transporters are therefore a kind of brake. If this return transport is now inhibited by the SNRI, more serotonin or noradrenaline molecules reach the second nerve cell and can develop their effect there. In this way, the serotonin norepinephrine reuptake inhibitors counteract the lack of serotonin and norepinephrine between the two nerve cells that is the cause of the depression.

Several active ingredients are approved in Germany; they differ mainly in their effect on norepinephrine levels. The names of the active ingredients are venlafaxine, duloxetine and milnacipran.

Find out all about the topic here: Drugs for depression.

Side effects of SNRI

An increase in the serotonin and especially the noradrenaline level in the synaptic gap leads to an increase in the activity of the sympathetic nervous system. This is understood to be a system of nerve cells that controls basic body functions and - from an evolutionary perspective - has the task of preparing the body for fight, flight or similar stressful situations. Therefore, in addition to an increase in heart rate and blood pressure, the effects of increased sympathetic activity also include increased sweat flow as well as sleep disorders and restlessness. Other possible side effects that are based on an increase in sympathetic activity are dry mouth, nausea or urination disorders and possibly sexual dysfunction.

In particular because of the increase in serotonin activity in the synaptic gap, many patients complain of nausea and vomiting at the beginning of treatment with serotonin-noradrenaline reuptake inhibitors. In most cases, however, these symptoms go away very quickly and can be treated temporarily with anti-nausea drugs known as antiemetics.

Caution is advised when serotonin-norepinephrine reuptake inhibitors are combined with other medications, as interactions can then occur in certain cases. Other psychotropic drugs should primarily be mentioned here, i.e. drugs that are used for mental illnesses such as depression. For this reason, monotherapy, i.e. therapy with only a single drug (e.g. SNRI), is generally recommended for the treatment of depression. In particular the combination with the so-called MAOIs, another group of antidepressants, or with triptans (Migraine therapy) should be avoided at all costs, as the effects of the two drugs on serotonin activity add up and can lead to the dangerous picture of serotonin syndrome with confusion, seizures or even coma.

If the serotonin-norepinephrine reuptake inhibitors are discontinued too abruptly when the therapy is ended, withdrawal symptoms such as circulatory problems, sleep or digestive disorders and the like can result. come. Due to their effect on the central nervous system, active driving under treatment with serotonin-noradrenaline reuptake inhibitors should be temporarily avoided.

You might also be interested in these topics:

• The side effects of antidepressants
• The serotonin syndrome

Do SNRIs lead to weight gain?

Due to the increasing effect of the serotonin-noradrenaline reuptake inhibitors on the sympathetic activity, many patients tend to lose weight under treatment with SNRI. This is particularly noteworthy since weight gain is one of the most common side effects of another large group of antidepressants tricyclic antidepressants (e.g .: amitriptyline), belongs. This difference should therefore be taken into account if the patient whose depression is to be treated is overweight.
In rare cases, however, patients react to the use of SNRI with weight gain - in this case, consideration should be given to accepting the weight gain for the limited period of the SNRI therapy.

Due to the rather favorable effect of the serotonin norepinephrine reuptake inhibitors on the patient's weight, SNRIs are not only suitable as the first choice medication for depression, but can also serve as an alternative for patients who were initially treated with tricyclic antidepressants or mirtazapine and have developed weight gain with this therapy.

Read more on the subject below Antidepressants without weight gain.

When should SNRIs not be given?

SNRIs must not be used if an intolerance and allergic reaction to the active ingredient has occurred. The intake of so-called MAOIs, the irreversible monoamine oxidase inhibitors, is also considered a strict contraindication. These are drugs used to treat depression or Parkinson's disease. Taking it at the same time or taking it less than two weeks ago can lead to life-threatening side effects. The group of MAOIs includes active ingredients such as tranylcypromine or selegelin.
Particular caution is required if other substances that act on the serotoninergic system are taken in addition to the SNRI. This can lead to the so-called serotonin syndrome, which is sometimes life-threatening.

Patients with increased intraocular pressure, high blood pressure, or heart problems are also advised to take increased caution when taking SNRIs. Blood clotting disorders, increased cholesterol levels and diabetes are also relative contraindications. Patients who suffer from the diseases mentioned or who are taking medication should inform their doctor about this. They will carefully weigh the benefits and risks and, if necessary, adjust the prescription.

Find out more about the topic here: MAO inhibitors.

What is the difference to the SSRIs?

Nowadays, in addition to the SNRI, mainly the so-called SSRIs are used in the therapy of depression. SSRI stands for Selective Serotonin Reuptake Inhibitor. Representatives of this group are, for example, the active ingredients fluoxetine, fluvoxamine, paroctein, setralin, citalopram or escitalopram.

SSRIs act on the serotoninergic system, they inhibit the reuptake of serotonin and thereby strengthen its effect. SNRIs also act on serotonin transporters, but also on the reuptake of norepinephrine. There is no clear evidence that SNRIs are more effective than SSRIs; the choice of drug determines the indication and tolerability. In general, patients who want an increase in drive tend to prefer the SNRI, as norepinephrine apparently has a positive influence on the energy level and alertness. Patients with suicidal ideation are advised not to use the SNRI, as the risk of suicidal behavior can be increased by the medication.

How patients react to the respective antidepressant is very individual and depends on various factors. Some patients show intolerance to a certain group, so a change may be advisable. Patients should work with their doctor to find an effective and well-tolerated drug.

Find out all about the topic here: SSRI.

SNRI in combination with alcohol

Alcohol is an important issue in the context of depression. Many alcoholics are depressed and many people who suffer from depression drink bottles. The mechanism behind this vicious circle becomes apparent when looking at the processes in our nervous system: Alcohol counteracts the serotonin deficiency underlying depression in the short term by increasing the serotonin level in the central nervous system. In this way, the mood of the patients is improved and sociability is promoted - this is precisely what is perceived as very pleasant by depressed patients, since social contacts often also suffer from depression. However, regular alcohol consumption leads to an additional reduction in serotonin levels in the long term. To combat this heightened depression, the patient starts drinking again, and so on - the vicious circle is in full swing.

It is precisely this mechanism that makes alcohol consumption a sensitive issue in depressed people. Actually, as in general with all psychotropic drugs, the consumption of alcohol should be strictly avoided when treating with serotonin-norepinephrine reuptake inhibitors. Otherwise, the effects of alcohol and SNRI on the central nervous system can add up in the long term and lead to serious interactions. It can include seizures and in extreme cases even death. Therefore, depressed patients with alcohol dependence should not only initiate depression therapy, but also alcohol withdrawal and therapy.

Read more on the subject below Antidepressants and alcohol - are they compatible?

SNRI during pregnancy

pregnancy and Antidepressants are two closely related topics, as numerous studies have shown that the occurrence of Depression in pregnant women as well as women in Puerperium is significantly increased compared to the general population. The most important advice in connection with pregnancy during treatment for depression: be sure to tell your doctorthat you are pregnant or planning to become pregnant! Lots of antidepressants are viz unsuitable for pregnant women, and the serotonin-norepinephrine reuptake inhibitors in particular should only be used in pregnant women extremely careful can be used. Especially in the late phase of pregnancy, taking SNRIs can namely in the child to a variety of symptoms that occur after childbirth. This includes sleep- and Breathing disorders, Seizures or a increased blood pressure.

For this reason, if you are pregnant with depression, you should first try all options non-drug treatment be exhausted. Here's primarily that psychotherapy to mention, as also herbal remedies like Johannis herbs are not considered to be completely unproblematic during pregnancy. No way however, the patient should receive ongoing drug therapy if pregnancy occurs cancel by hand! As already indicated above, should in this case inform a doctor immediately who can then make an informed decision about further treatment for depression during pregnancy, taking all aspects into account.

But now the pregnant patient suffers very severe depression, which can no longer be controlled without drug treatment, should rather rely on Selective Serotonin Reuptake Inhibitors (SSRIs) such as Citalopram or an active ingredient from the group of Tricyclic antidepressants can be used as serotonin-norepinephrine reuptake inhibitors. Although these are also not safe for the child, they have been much better investigated with regard to their potential for harm during pregnancy than the less frequently used SNRIs and, in moderate doses, contain them relatively manageable risk for harm to the child.

Even during the Lactation the intake of serotonin noradrenaline reuptake inhibitors poses a problem. The active ingredient can namely pass into breast milk and can thus lead to similar symptoms when transmitted to the child during breastfeeding as when transmitted during pregnancy (see above). So should Patient and doctor together Weighing up between breastfeeding and avoiding antidepressants on the one hand, or dieting with industrial baby food and the use of antidepressants on the other. In order to make a decision, it should be asked how severe the depression is in the mother and how good she is with it non-drug measures (Psychotherapy, natural remedies) can be controlled and, on the other hand, how important breastfeeding is to the mother. However, new studies indicate that low doses of serotonin-norepinephrine reuptake inhibitors pose no risk to the child from breastfeeding.

What should be considered when stopping?

Patients treated with SNRIs should not stop taking or change the dose without consulting their doctor. SNRI should never be stopped suddenly. This can lead to the occurrence of up to life-threatening side effects. These include symptoms such as tiredness, dizziness, headaches, drowsiness or confusion, diarrhea, nausea, nervousness, restlessness or abnormal sensations. Seizures are also possible if the drug is suddenly stopped.

These side effects are also known as withdrawal syndrome or withdrawal syndrome when stopping psychotropic drugs. In consultation with your doctor, the dose of the drug should be reduced gradually. If severe side effects occur, a doctor must be consulted.

What is withdrawal syndrome?

Withdrawal syndrome or withdrawal syndrome describes the occurrence of various side effects after stopping or reducing the dose of antidepressants. The withdrawal syndrome also occurs when the SNRI is discontinued; the active ingredient venlafaxine is at very high risk.

The clinical picture of withdrawal syndrome is diverse, in addition to perceptual disorders such as abnormal sensations, ringing in the ears or double vision, balance disorders and sleep disorders can occur. Psychological symptoms such as increased irritability, anxiety or depressive moods are also possible. Physical symptoms may also occur, including headache, tremors, sweating, or loss of appetite. These symptoms appear shortly after you stop taking the drug or reduce your dose and resolve quickly when you start taking the drug again.

To prevent withdrawal syndrome, SNRIs should never be stopped independently without consulting a doctor. In addition, antidepressants should never be stopped suddenly; the tapering should last for at least two, preferably four weeks.

Price from SNRI

The prices of the drugs vary depending on the active ingredient, provider and pack size. In addition, the cost depends on the individually prescribed daily dose.

Venlafaxine in a pack of 100 tablets with an active ingredient content of 75 milligrams Venlafaxine costs around € 40. Duloxetine in the 28-piece pack with 20 mg about 37 €. Milnacipran in a pack of 50 with 50 mg cost 47 €.

The effectiveness of the pill while taking an SNRI

There is no evidence of the reduced effectiveness of oral contraceptives in preventing unwanted pregnancies due to the use of substances from the SNRI group. Women taking SNRIs should use effective contraception as the drug can potentially pose risks to the unborn child.