Depresil

Approved Indications:

• Depression: Particularly for mild to moderate cases, including somatic (non-psychotic) symptoms.
• Anxiety Disorders: Generalized anxiety, psychosomatic anxiety, and mixed anxiety-depression states.
• Psychogenic Dizziness and Fatigue: Especially where linked to functional or neurotic disorders.
• Psychosomatic Disorders: Such as irritable bowel syndrome (IBS), tension-type headache, and chronic pain with depressive features.
• Neurasthenia: Especially when associated with fatigue, anxiety, and depressive mood.
• Adjustment Disorders: With depressive or anxious symptoms.

Off-label or Clinically Accepted Uses:

• Menopausal syndrome-related mood disturbances
• Functional gastrointestinal disorders with mood symptoms
• Chronic fatigue syndrome with comorbid anxiety or depression
• Post-stroke depressive symptoms (select cases)

Route of Administration: Oral
Formulation: Tablet (commonly contains Flupentixol 0.5 mg + Melitracen 10 mg per tablet)

Adults:

• General dosage: 1 tablet twice daily (morning and early afternoon).
• If needed, the dose may be increased to 2 tablets twice daily for more severe symptoms.
• Dosage should be tailored to individual response.

Pediatrics:

• Not recommended due to limited safety data and risk of extrapyramidal symptoms.

Elderly:

• Use with caution; start with the lowest effective dose (e.g., 1 tablet daily) due to increased sensitivity and risk of side effects.

Hepatic Impairment:

• Use with caution; dose adjustment may be necessary. Monitor liver function periodically.

Renal Impairment:

• Generally, no adjustment required, but clinical monitoring is advised in severe cases.

Treatment Duration:

• Continue for several weeks or until symptom resolution. Gradual discontinuation is recommended to avoid withdrawal effects.

Flupentixol + Melitracen is a fixed-dose combination that synergistically targets both mood and anxiety symptoms. Flupentixol is a thioxanthene-class antipsychotic with low-dose anxiolytic and mood-stimulating properties. It acts by antagonizing dopamine D1 and D2 receptors, which helps stabilize mood and reduce psychomotor retardation. Melitracen is a tricyclic antidepressant (TCA) that inhibits the reuptake of norepinephrine and serotonin, increasing their availability in the synaptic cleft and enhancing mood. The combination provides a rapid onset of anxiolytic and antidepressant effects with minimal sedation and is effective in psychosomatic conditions with underlying mood symptoms.

Flupentixol:

• Absorption: Well absorbed orally; bioavailability ~40–50%.
• Onset: Therapeutic effects typically within 2–3 days when combined with Melitracen.
• Distribution: Highly protein-bound (~98%)
• Metabolism: Hepatic via CYP2D6
• Half-life: ~35 hours
• Excretion: Mainly via urine and feces

Melitracen:

• Absorption: Rapid oral absorption; bioavailability ~50–60%
• Distribution: Lipophilic; crosses the blood-brain barrier effectively
• Metabolism: Extensively metabolized in the liver
• Half-life: ~19 hours
• Excretion: Primarily renal, with minimal unchanged drug in urine

Pregnancy:

• No formal FDA pregnancy category assigned.
• Use during pregnancy only if clearly needed. Tricyclic antidepressants may pose potential risk in the third trimester, such as neonatal withdrawal or respiratory distress.

Lactation:

• Both components may be excreted in breast milk in small amounts.
• Use with caution in breastfeeding mothers. Monitor infants for sedation, feeding problems, or irritability.

• Primary Class:
  • Flupentixol – Antipsychotic (low-dose, typical)
  • Melitracen – Tricyclic Antidepressant (TCA)
• Combination Class:
  • Anxiolytic-antidepressant fixed-dose combination for functional and psychosomatic disorders

• Hypersensitivity to Flupentixol, Melitracen, or any excipients
• Manic episodes or bipolar mania
• Severe hepatic impairment
• Narrow-angle glaucoma (due to anticholinergic effects of Melitracen)
• Pheochromocytoma
• Concomitant use with MAO inhibitors or within 14 days of discontinuation
• History of seizure disorders (relative contraindication due to TCA component)

• Suicidal Ideation: Risk in early treatment, especially in young adults; close monitoring required.
• Seizure Risk: Use with caution in patients with epilepsy or predisposition to seizures.
• Cardiovascular Caution: TCAs may cause QT prolongation, orthostatic hypotension, and conduction disturbances.
• Urinary Retention and Glaucoma: Anticholinergic effects of Melitracen may exacerbate these conditions.
• Hepatic Monitoring: Recommended in long-term use or pre-existing liver disease.
• Extrapyramidal Symptoms (EPS): Risk increases with higher doses or in elderly.
• Avoid Alcohol: CNS depressant effects may be enhanced.
• Gradual Withdrawal: To minimize rebound symptoms or discontinuation syndrome.

Common Side Effects:

• Central Nervous System:
  Drowsiness, insomnia, dizziness, headache, agitation
• Gastrointestinal:
  Dry mouth, constipation, nausea
• Cardiovascular:
  Orthostatic hypotension, palpitations, tachycardia
• Others:
  Weight gain, blurred vision, sweating

Serious Side Effects:

• Neurological:
  Extrapyramidal symptoms (tremor, rigidity)
  Seizures (rare)
• Cardiac:
  QT prolongation, arrhythmias (dose-dependent)
• Psychiatric:
  Mania in predisposed individuals
• Hypersensitivity Reactions:
  Skin rash, angioedema (rare)

Onset & Severity:
Mild side effects generally appear within the first week. EPS and cardiovascular side effects may be dose-dependent and require clinical monitoring.

Major Drug Interactions:

• MAO Inhibitors: Risk of serotonin syndrome or hypertensive crisis—contraindicated.
• CNS Depressants (alcohol, benzodiazepines): Additive sedation.
• Anticholinergics: May enhance dry mouth, blurred vision, urinary retention.
• Antihypertensives: Enhanced hypotensive effects.
• QT-prolonging agents (e.g., antiarrhythmics, macrolides): Risk of cardiac arrhythmia.
• SSRIs/SNRIs: May increase serotonin activity—use caution.
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May increase Flupentixol levels.

Enzyme Involvement:

• Metabolized primarily by CYP2D6 (Flupentixol) and other hepatic enzymes (Melitracen)

• Recent Clinical Focus:
  Expanded use in functional somatic syndromes and psychosomatic illnesses due to dual mechanism and rapid onset.
• Guideline Positioning:
  Not included in major international depression treatment guidelines (e.g., NICE, APA) but recognized in several European and Asian protocols for anxiety-depression overlaps.
• Regulatory Status:
  Approved in many countries (Europe, Asia, Latin America); not FDA-approved in the USA but widely used globally under various brand names (e.g., Deanxit).
• Monitoring Update:
  Emphasis on periodic cardiac and hepatic monitoring, especially in long-term use or elderly patients.

• Storage Temperature:
  Store below 25°C (77°F)
• Light & Humidity Protection:
  Protect from moisture and direct sunlight. Keep in original blister packaging.
• Handling Precautions:
  Do not freeze. Keep out of reach of children.
• Shelf-life:
  Follow expiration date printed on packaging; typically 24–36 months unopened.