Tricylic Compounds include-
      Tertiary amines - Amitriptyline,Clomipramine,Doxepin,Imipramine,Trimipramine
      Secondary amines - Amoxapine, Desipiramine, Nortriptyline,Portriptyline
      Refer - Amitriptylin

Interacting drugs - summary

+ Doxipin

  Alcohol -  alcohol ingestion exacerbate the potential sedative effects of doxepin

Cimetidine -  Serious anticholinergic symptoms with elevated TCAs levels

MAO inhibitors -  serious side effects and even deaths have been reported

.

     Tricylic Compounds include-
      Tertiary amines - Amitriptyline,Clomipramine,Doxepin,Imipramine,Trimipramine
      Secondary amines - Amoxapine, Desipiramine, Nortriptyline,Portriptyline
      Refer - Amitriptylin

Doxepin cream-

Systemic-

Most common- Drowsiness,dizziness,dry mouth,thirst, headache, fatigue, dizziness, emotional changes taste changes, nausea, anxiety, fever, insomnia, confusion,headache, rashes.

Local- the most common local effect was burning or stinging at theapplication site.

Other effects include-pruritus or eczema,exacerbation, dryness/lightness of skin, paresthesias, edema, irritation, tingling, scaling, cracking

Glaucoma,neonates,suscesptibilty to urinary retension.

Special precautions:

Epilepsy,hypertension,cardiovascular disease.

Warnings-

Doxepin cream-

For external use only- Topical preparation-. Do not use ophthamically , orally, or intravaginally.

Drowsiness - occurs in 20% of the patients treated with doxepin cream, especially for patients receiving treatment to > 10% of body surface area.

Warn patients of this possibility and caution them against driving a motor vehicle or operating hazardous machinery while being treated with doxepin cream. also warn patients that effects of alcoholic beverages can be potentiated when using doxepin cream.

If excessive drowsiness occurs it may be necessary to reduce the number of applications, the amount of cream applied or the percentage of body surface area treated.

Pregnancy- use during pregnancy only if clearly needed.

Lactation- because of the potential for serious advese reactions innursing infants, decide whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Children- safety and efficacy in children have not been established.

Indications:

Depression

Dosage::

Individualise dose. Maximum recommended dose is 150mg/day, given at bed time.

Start with 75mg/day. Optimum dose is 75 to 150mg/day.

Overdosage- Symptoms -

Mild- drowsiness,stupor, blurred vision, excessive dryness of mouth

Severe- respiratory , hypotension, coma, convulsions, cardiac arrhythmias,tachycardias, urinary retention, (bladder atony), decreased GI motility (parlytic ileus) hyperthermia, hypothermia, hypertension, dilated pupils hyperactive reflexes.

Treatment-

1. Mild - observation and supportive therapy is all that is necessary

. 2. Topical prepn.- It may be necessary to reduce the percent of body surface area treated or frequency of application or apply thinner layer of cream.

3. Severe- management consists of aggressive supportive therapy. Throughly wash the area treated with cream.

4. Establish an adequate airway in comatose patients and use assisted ventilation if necessary.

5. ECG monitoring may be required for several days because relapse after apparent recovery has been reported with oral doxepin.

6. Treat arrhythmias with the appropriate antiarrhythmic agent

7. Dialysis and forced diuresis generally are not of value due to high tissue andprotein binding of doxepin

Missed dose-

 1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

EVIDENCE BASED MEDICINE (MIMS- April 2003)

Depression

Comparitive effectiveness of various interventions

Beneficial

1. Tricyclic and heterocyclic antidepressants

2. Selective serotonin reuptake inhibitors and related drugs

3. Monamine oxidase inhibitors

4. Interpersonal therapy (mild to moderate depression)

Likely to be beneficial

1. St.Johns wort in mild to moderate depression

2. Problem solving therapy in mild to moderate depression

3. Combining drug psychological treatment in severe depression

4. Maintenance drug treatment may prevent recurrence

Unknown efectiveness -

1. Excercise

2. Bibliotherapy (advising patients to read material on mood therapy)

3. Non-directive counselling

4. Psychological treatment in severe depression

5. Clinician colloboration and patient education.

KEY POINTS

1. Several treatments are effective in the treatment of mild to moderate depression. These include anti-depression drugs, cognitive therapy and interpersonal therapy. Less robust RCTs have found that problem solving therapy and St Johns wort are also effective.Specific psychological treatments such as cognitive and interpersonal therapy have been shown to be as effective as drugs and there is no significant difference between anti-depressant drugs, although they vary in adverse effects and costs.

2. There is limited evidence that other treatments such as excercise, bibliography and non-directive counselling may be effective, but further research is needed.

3. There is no reliable evidence that one type of treatment (drug or non-drug) is superior to another. Limited evidence suggest that combing drug and psychological treatments may be effective in severe but not in moderate depression.

4. Of the interventions examined, anti-depressants drugs are the only treatment for which there is good evidence of effectivenes in severe psychotic depressive disorders. There are no trials comparing drug and non-drug treatments in severe depressive disorder.

5. Continuing anti-depressants drug treatment for four to five months after recovery reduces the risk of relapse, and maintenace therapy in recurrent depressive disorder reduces the risk of recurrence.

6. There is no evidence of a difference in long-term benefits between treatments

Tricylic Compounds include-
      Tertiary amines - Amitriptyline,Clomipramine,Doxepin,Imipramine,Trimipramine
      Secondary amines - Amoxapine, Desipiramine, Nortriptyline,Portriptyline
      Refer - Amitriptylin

 AVOID CONCURRENT USE WITH ERYTHROMYCIN

Doxepin/Doxepin cream-

 1. Caution patients about operating hazardous machinery including automobiles , until they are reasonably certain that doxepin therapy does not adversely affect their ability to engage in such activities

2. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to Doxepin. Also tell your doctor if your are allergic to any other substances such as foods, preservatives or dyes.

3. Pregnancy- doxepin has not been shown to cause birth defects or other problems in animal studies

4. Breast feeding- Be sure you have discussed the benefits the risks and benefits of this medicine with your doctor.

5. Children- no specific information available comparing use of doxepin in children with use in other age groups

6. Elderly- this medicine has not been shown to cause different side effects or problems in older people than in adults

7. Other medicines- tell your doctor if you are taking any of the following-

Alcohol or CNS depressants ( causing drowsiness )or Tricyclic antidepressants or Drinking alcohol or using these medicines with topical doxepin may cause increased CNS depressiant effects such as drowsiness

Cimetidine or Debrisoquine or Medicines that correct heart rhythm problems, - using these medicines may increase the chance of side effects

Monoamie Oxidase inhibitors- using topical doxepin wghile you are taking or within 2 weeks of taking MAO inhibitors may cause sudden high body temperature ,excitability , severe convulsions, and even death, however sometimes some of these medicines may be used together under close supervision by your doctor

8. Other medical - Glaucoma or Urinary tract blockage or difficult urination- using topical doxepin maymake these conditions worse.

9. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

Refer amitriptyline

Reports not available.

Pregnancy-

Use during pregnancy only if clearly needed.

Lactation-

Because of the potential for serious advese reactions innursing infants, decide whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Children-

Safety and efficacy in children have not been established.