Mianserin

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Contents

[edit] BRAND NAMES

  • Others: Lerivon (Argentina, Belgium, Czech Republic, Poland, Slovakia)

[edit] STRUCTURE

Mianserin.jpg

[edit] MECHANISM OF ACTION

Mianserin is a noradrenergic and specific serotonergic antidepressant (NaSSA). It increases central noradrenergic and serotonergic release by presynaptic central alpha2-autoreceptor blockade.

Moreover, it possesses anxiolytic and sleep improving properties, which are of value in treating patients with anxiety or sleep disturbances associated with depressive illness. The histamine H1 and alpha1-antagonistic activity of Mianserin is thought to be responsible for its sedative properties.

Mianserin lacks any anticholinergic properties.


Pharmacokinetics

After oral administration, mianserin is rapidly and well absorbed, reaching peak plasma levels within 3 hours. The bioavailability is approx. 20%.

Binding of mianserin to plasma proteins is approx. 95%. The half-life of elimination (21-61 hours) is sufficient to justify once-a-day dosing. Steady-state plasma levels are reached within 6 days. Mianserin is extensively metabolized and eliminated via the urine and faeces within 7-9 days. Major pathways of biotransformation are demethylation and oxidation, followed by conjugation.

[edit] INDICATIONS

For relief of symptoms of depression in those cases of depressive illness where drug therapy is indicated.

[edit] DOSAGE

The daily dose can be taken either in divided doses or preferably (in view of a favourable effect on sleep) as a single dose at night. Treatment with an adequate dose should result in a positive response within 2-4 weeks. In case of an insufficient response the dose can be increased. If there is no response within a further 2-4 weeks, then treatment should be stopped.

It is recommended to maintain antidepressant treatment for 4-6 months after clinical improvement has occurred.


Adults: Dosage should be individually determined. Treatment should begin with 30 mg daily and dosage should be adjusted according to the clinical response. The effective dose usually lies between 30 and 90 mg (mostly 60 mg) daily.

Elderly: Dosage should be individually determined. Not more than 30 mg daily initially. The dose should be slowly increased under close supervision. A dose lower than is usual for adults may be sufficient for a satisfactory clinical response.

Children: Mianserin should not be used in patients under 18 years of age unless under the supervision of a specialist.

[edit] CONTRAINDICATIONS

  • Mania.
  • Severe liver disease.
  • Hypersensitivity to mianserin or to any of the excipients.
  • Concomitant use of mianserin with monoamine oxidase (MAO) inhibitors (see Interactions).
  • Mianserin is contraindicated for the treatment of depression in patients 12 years of age and under.
  • Mianserin is contraindicated for the treatment of nocturnal enuresis.

[edit] WARNINGS AND PRECAUTIONS

  • Use in Children and Adolescents Under 18 Years of Age : Mianserin should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
  • Clinical Worsening and Suicide Risk: Patients of any age with Major Depressive Disorder or patients with a history of suicide events or those exhibiting a significant degree of suicidal ideation, may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Patients should be closely monitored, especially at the beginning of therapy or when the dose is changed, until such improvement occurs.
  • Mania and Bipolar Disorder : A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with any antidepressant alone may increase the likelihood of a mixed/manic episode in patients at risk for bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder. It should be noted that Mianserin is not approved for use in treating bipolar depression.
  • Cardiovascular disorders : QT prolongation and ventricular arrhythmias (including Torsades de Pointes (TdP)) have been reported during the post-marketing use of mianserin. Mianserin should be used with caution in patients with risk factors for QTc prolongation/TdP including congenital long QT syndrome, age >65 years, female sex, structural heart disease/LV dysfunction, medical conditions such as renal or hepatic disease, use of medicines that inhibit the metabolism of mianserin, and the concomitant use of other QTc prolonging medicines. Hypokalaemia and hypomagnesaemia should be corrected prior to treatment. Consideration should be given to stopping mianserin treatment or reducing the dose if the QTc interval is >500ms or increases by >60ms.
  • Patients with narrow angle glaucoma or symptoms suggestive of prostatic hypertrophy should also be monitored even though anticholinergic side effects are not anticipated with Mianserin therapy.
  • Bone marrow depression, usually presenting as granulocytopenia, agranulocytosis and thrombocytopenia has been reported during treatment with Mianserin. Because most of the cases occurred in the first three months of treatment, the Medicines Adverse Reactions Committee has recommended that there should be intensive clinical monitoring of the patient in the first three months with blood counts at a minimum of once per month. These effects have been observed in all age groups but appear to be more common in the elderly. Patients should be warned to report symptoms or signs of sore throat, mouth ulcers, bowel upset or fever, stomatitis or other signs of infection and to stop the medication immediately and to seek a consultation with the prescribing doctor. If a patient experiences these effects treatment should be stopped and a full blood count should be obtained.
  • Treatment should be discontinued if jaundice occurs.
  • Treatment should be discontinued if convulsions occur.

[edit] INTERACTIONS

  • Patients should be advised to avoid taking alcohol during treatment.
  • CYP2D6 inhibitors would likely raise plasma levels of mianserin and hence could lead to mianserin toxicity.
  • CYP2D6 inducers would likely lead to reduced mianserin plasma concentrations and hence potentially diminish the therapeutic effects of mianserin
  • Concomitant treatment with antiepileptic drugs that are CYP 3A4 inducers (like phenytoin and carbamazepine), can result in reduced plasma levels of mianserin.
  • The risk of QTc prolongation and/or ventricular arrhythmias (e.g. Torsades de Pointes) is increased with concomitant use of other medicines which prolong the QTc interval ( e.g. some anti-psychotics and antibiotics).

[edit] PREGNANCY AND LACTATION

Although animal experiments indicate that Mianserin does not cause fetal harm and is excreted in the milk in very small amounts, the data in humans is limited and adverse effects have been seen with the use of other antidepressants. The benefits of the use of Mianserin during pregnancy or breast-feeding should be weighed against the possible hazards to the fetus or the newborn child.

[edit] SIDE EFFECTS

Common (> 1%)

  • Weight gain
  • Sedation/Somnolence/drowsiness (occurring at initiating of treatment and decreasing as treatment continues)
  • Elevated liver enzymes


Uncommon (0.1 – 1%)

  • Hypotension
  • Exanthema
  • Arthralgia


Rare (< 0.1%)

  • Disturbances of liver function (including jaundice)
  • Seizures
  • Neuroleptic malignant syndrome (NMS)
  • Restless legs
  • Bradycardia after the initial dose
  • Blood dyscrasias, usually presenting as granulocytopenia or agranulocytosis

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

http://www.medsafe.govt.nz/profs/datasheet/t/Tolvontab.pdf

[edit] REFERENCES

Antidepressants
Tricyclic antidepressants Amitriptyline (Elavil, Laroxyl)   Clomipramine (Anafranil)   Doxepin (Sinequan)   Imipramine (Tofranil)   Nortriptyline (Aventyl, Pamelor)   Trimipramine (Surmontil)
Selective serotonin reuptake inhibitors (SSRIs) Citalopram (Celexa, Seropram)   Escitalopram (Cipralex, Lexapro)   Fluoxetine (Prozac)   Fluvoxamine (Luvox, Maveral)   Paroxetine (Paxil, Seroxat)   Sertraline (Zoloft)
Serotonin–norepinephrine reuptake inhibitors (SNRIs) Desvenlafaxine (Pristiq)   Duloxetine (Cymbalta, Xeristar)   Venlafaxine (Efexor, Effexor)
Serotonin antagonists and reuptake inhibitors (SARIs) Trazodone (Desyrel, Oleptro)
Norepinephrine reuptake inhibitors (NRIs) Maprotiline (Ludiomil)   Reboxetine (Edronax)
Norepinephrine-dopamine reuptake inhibitors (NDRIs) Bupropion (Wellbutrin)
Noradrenergic and specific serotonergic antidepressants (NaSSAs) Mianserin (Lantanon)   Mirtazapine (Remeron)
Norepinephrine-dopamine disinhibitors (NDDIs) Agomelatine (Valdoxan, Thymanax)
Monoamine oxidase inhibitors Nonselective Tranylcypromine (Parnate)
Monoamine oxidase inhibitors B-Selective Selegiline (Transdermal) (Emsam)
Others 5-Hydroxytryptophan   S-Adenosyl methionine   Hypericum (St John's wort)