Milnacipran

Milnacipran is an active substance that is used to treat depression. It belongs to the group of serotonin-norepinephrine reuptake inhibitors (SNRIs). Milnacipran is usually available as milnacipran hydrochloride, is a white crystalline powder and is readily soluble in water. The active substance is a racemic 1:1 mixture consisting of the 1R,2S isomer and the 1S,2R isomer. A racemate is an active substance that consists of 2 molecules that occur in a 1:1 ratio and behave like image and mirror image. One speaks of the R-(dextrorotatory) enantiomer and S-(levorotatory) enantiomer. Enantiomers do NOT differ in their physical properties such as melting or boiling point. However, they can behave in opposite ways in terms of their effects. For example, (S)-carvone smells like caraway and (R)-carvone smells like mint. The amino acid (S)-valine tastes bitter, while (R)-valine tastes sweet. For these reasons, both enantiomers are always tested in today's approval procedures for new active ingredients. Sometimes one enantiomer can be converted into the other in the body.

Milnacipran works by inhibiting the reuptake of serotonin and noradrenaline into the presynapse. This increases the concentration of the two messenger substances (neurotransmitters) in the synaptic cleft. The exact pathological mechanism of depression is not yet fully understood. However, it is assumed that the concentrations of the neurotransmitters serotonin and noradrenaline play a decisive role. The reuptake inhibition increases the concentration in the cerebrospinal fluid.

Milnacipran is metabolized in the liver, mainly by the CYP3A4 enzyme. The bioavailability, i.e. the percentage of the active substance available in the blood, is 85-90%. The half-life, i.e. the time the body needs to excrete half of the active substance, is around 6-8 hours. The maximum plasma concentration (Cmax), i.e. the maximum concentration of the active substance in the blood plasma (liquid cell-free part of the blood) is 341 ng/mL and is reached after approx. 6-8 hours.

Always take Milnacipran exactly as described in the package leaflet or as advised by your doctor.

Adults:

The usual recommended dose is 100 mg per day, divided into 50 mg in the morning and 50 mg in the evening.

The dose should be reduced for patients with renal insufficiency.

As with other antidepressants, the optimum effect of milnacipran is only achieved after 1-3 weeks.

Milnacipran should not simply be discontinued, but phased out, i.e. the dose should be reduced slowly. Your doctor will know how to discontinue the medication.

The following side effects may occur:

Very common:

• Headache
• Nausea

Common:

• Fatigue
• Testicular pain
• Erectile dysfunction
• Ejaculation disorders
• Pain when urinating
• Frequent urination of small amounts
• Pain in the skeletal muscles
• Itching
• skin rash
• Excessive sweating
• constipation
• diarrhea
• abdominal pain
• stomach pain
• vomiting
• Dry mouth
• hot flushes
• high blood pressure
• palpitations
• Rapid heart rate
• Somnolence
• Sensory disturbances (e.g. tingling)
• dizziness
• trembling
• migraine
• Suicidal behavior
• Sleep disorders
• Eating disorders
• Depression
• Anxiety
• Agitation

Occasionally:

• Hypersensitivity
• Increased blood lipid levels
• weight loss
• panic attacks
• confusion
• delusions
• hallucinations
• Manic episodes
• Decreased libido
• nightmares
• suicidal thoughts
• memory disorders
• compulsive urge to move
• balance disorders
• taste disturbances
• fainting spells
• dry eyes
• eye pain
• pupil dilation
• lens adaptation disorders
• blurred vision
• visual deterioration
• Noises in the ears
• Irregular electrical activity of the heart
• cardiac arrhythmia
• myocardial infarction
• Raynaud's syndrome
• Low blood pressure
• orthostatic hypotension
• cough
• breathing difficulties
• dry nose
• difficulty swallowing
• intestinal inflammation
• gastritis
• gastrointestinal mobility disorders
• flatulence
• Stomach and intestinal ulcers
• inflammation of the oral mucosa
• elevated liver enzymes
• hives
• skin inflammation
• skin diseases
• muscle stiffness
• muscle pain
• Urine discoloration
• Urinary incontinence
• urinary retention
• Absence of menstruation
• heavy periods
• menstrual cramps
• intermenstrual bleeding
• Functional disorders of the prostate
• Fever attacks
• breast pain
• chills
• discomfort
• Feeling ill

Rarely:

• allergic shock
• Inadequate ADH secretion
• loss of reality
• abnormal thinking
• Psychotic disorders
• cerebrovascular disorders
• movement disorders
• Parkinsonism
• seizures
• heart failure
• liver inflammation
• liver damage
• Photosensitivity reaction

Frequency unknown:

• Bleeding of the skin and mucous membranes
• Decreased sodium ion concentration in the blood
• aggression
• serotonin syndrome
• Tako-Tsubo cardiomyopathy
• Stevens-Johnson syndrome
• Bleeding after birth

Interactions may occur if the following medicines are taken at the same time:

• irreversible monoamine oxidase inhibitors (MAO inhibitors) (iproniazid)
• selective MAO-B inhibitors (selegiline)
• 5-HT1D agonists(sumatriptan and other triptans)
• Digitalis preparations (dioxin,...)
• Drugs that affect the cardiovascular system(adrenaline, noradrenaline, clonidine and others)
• other drugs for the treatment of depression (linezolid, moclobemide, toloxatone, methylene blue)
• Medications that increase the risk of bleeding (NSAIDs, aspirin)
• lithium
• diuretics

Milnacipran must NOT be taken in the following cases

• if you are allergic to milnacipran
• if taking irreversible MAO inhibitors
• when taking selective MAO-B inhibitors
• if you are taking medication for migraines
• if you are breastfeeding
• if you have high blood pressure
• if you have coronary heart disease
• if you are taking medication that affects the cardiovascular system
• if you are taking other medication for depression
• if you have an enlarged prostate

Milnacipran should NOT be used under the age of 18, as patients under the age of 18 are at increased risk of side effects such as suicide attempts, suicidal thoughts or hostility.

Milnacipran should NOT be used during pregnancy, as toxicity has been observed in animal studies and the risk of bleeding after birth increases.

Milnacipran should NOT be used during breastfeeding because it passes into breast milk.