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This is how duloxetine works
Nerve cells (neurons) in the brain communicate with each other using messenger substances (neurotransmitters): One cell releases certain neurotransmitters, which are then perceived by the next cell through docking points (receptors). Because the next cell can either be inhibited or excited (depending on the receptor and neurotransmitter) and a cell usually has connections (synapses) to many other neurons, this creates a highly complex network, which is only partially understood.
It has been shown that certain messenger substances usually cause a very specific effect. In the case of serotonin, commonly known as the “happiness hormone”, concentrations that are too low lead to depression, and concentrations that are too high lead to psychoses and delusions. Norepinephrine, on the other hand, is an exciting neurotransmitter that is responsible for activating certain areas of the brain.
In order to be able to precisely control the communication between the nerve cells, the nerve cell that emits the neurotransmitter continuously picks up the same again. This limits the time of the signal to the next cell. If this resumption is inhibited, as by the administration of duloxetine, the neurotransmitters linger longer on the receptors of the next nerve cell and thus have a stronger effect. A deficiency of serotonin and noradrenaline, which often manifests itself as depression or anxiety disorder, can thus be remedied or positively influenced.
The pain-relieving properties of duloxetine in the treatment of diabetic neuropathy and fibromyalgia result from the excitation of pain-relieving nerve pathways. Above all, this can normalize an over-sensitive pain threshold. Likewise, increased stimulation of the serotonin and norepinephrine system by duloxetine causes increased closure of the urethral sphincter, which can treat stress urinary incontinence.
Uptake, breakdown and excretion of duloxetine
After taking duloxetine, the active ingredient is absorbed into the blood through the intestines. The highest duloxetine blood level can be measured after six hours, with only about half of the active ingredient reaching the major bloodstream as it is partially broken down in the liver immediately after ingestion. The active ingredient duloxetine then reaches the brain via the bloodstream. Half of the ineffective breakdown products are excreted via the kidneys with the urine within twelve hours.
When is duloxetine used?
The active ingredient duloxetine is approved for the treatment of:
- Depression (so-called major depression)
- Diabetic neuropathic pain
The use of duloxetine for pain relief in fibromyalgia occurs in Germany "off-label", ie outside the approval area.
Treatment with duloxetine is usually long-term, but it should be checked at regular intervals whether the dose needs to be adjusted or whether the therapy is still necessary.
This is how duloxetine is used
The active ingredient duloxetine is taken in the form of capsules that contain enteric pellets and only release the active ingredient in the intestine. Depending on the area of application, 30 to 60 milligrams of duloxetine are taken once or twice a day. The maximum daily dose is 120 milligrams. For better tolerability, the treatment is started with a low dose and then gradually increased to the required final dose.
The capsule is swallowed with a glass of water with or without food. In the case of swallowing difficulties or feeding by tube, the duloxetine pellets can also be taken suspended in water, but must not be chewed under any circumstances.
To end the therapy, the duloxetine dose should be slowly reduced (so-called “tapering off” the dose), otherwise severe side effects can occur.
What side effects does duloxetine have?
Duloxetine side effects tend to be more pronounced at the beginning of treatment and get better over time. More than ten percent of those treated experience side effects such as headache, drowsiness, nausea and dry mouth.
About one in ten to one hundred patients report decreased appetite, insomnia, anxiety, decreased sexual desire (libido) and erectile dysfunction (impotence), dizziness, tremors, palpitations, ringing in the ears, blurred vision, increased blood pressure, indigestion and abdominal pain, sweating, rash , Muscle pain and cramps, weight loss and urinary retention.
What should be considered when taking duloxetine?
Duloxetine is broken down in the liver by certain enzymes (cytochrome P450 1A2 and 2D6), which also break down other drugs. If these are taken at the same time, the blood levels of the individual active ingredients can rise or fall. This applies, for example, to antidepressants such as fluvoxamine, amitriptyline, imipramine and desipramine, agents against an overactive bladder such as tolterodine and agents for the treatment of psychoses and schizophrenia such as risperidone.
Smokers break down duloxetine faster than non-smokers.
Medicines that increase the serotonin concentration in the brain should not be combined with duloxetine, as this can lead to a life-threatening serotonin syndrome. Medicines in question include MAO-type antidepressants (such as moclobemide or tranylcypromine), other antidepressants, St. John's wort supplements, migraine medications (such as sumatriptan and naratriptan), strong pain relievers (opioids such as tramadol, fentanyl, and pethidine), and serotonin precursors like tryptophan and 5-hydroxytryptophan (5-HTP).
The combination of duloxetine with anticoagulants such as phenprocoumon, warfarin and ASA / acetylsalicylic acid can change the blood clotting time, which is why it should be monitored closely. The dosage of the anticoagulant may need to be adjusted.
Like many other antidepressants, duloxetine can increase the risk of suicide, especially in adolescents. For this reason, duloxetine is only approved for people aged 18 and over and should not be used or only under medical supervision in patients with such inclination.
A reduced dose of duloxetine is recommended for patients with impaired liver or kidney function.
Duloxetine must not be used during pregnancy and breastfeeding as it can harm the child.
How to get medication with duloxetine
Preparations with duloxetine require a prescription in every dosage and for every purpose.
How long has duloxetine been known?
The antidepressant duloxetine was developed by scientists at the pharmaceutical company Eli Lilly and Company and a patent was applied for in 1986, which was granted in 1990. The first registration was granted in 2004 in the USA, later in the same year also in Germany. The patent expired at the beginning of 2014. Since then, several generics have come with the active ingredient Duloxetine on the market.
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