Depression 

Phenethylamine group - Venlafaxine 

Approved by FDA on December 28,1993

Special senses-

Blurred vision (6%), taste perversion ( 2% ), mydriasis ( 2%) Cardiovascular- Vasodilation ( 4% ) increased blood pressure /hypertension (2% ) ,tachycardia( 2%) postural hypotension.(1%)

CNS- Somnolence (23% ), dry mouth ( 22% ), dizziness, ( 19% )insomnia ( 18% ), nervousness,( 13%) anxiety, (6%) tremor (5%), abnormal dreams (4%), hypertonia, (3%) paresthesia, (3%) decreased libido (2%) , agitation,(2%) confusion,(2%) abnormal thinking (2%) depersonalization (1%) , depression, (1%) urinary retention (1%) twitching (1%)

GU- abnormal ejaculation/orgasm, (12%) impotence, (6%), urinary frequency impaired (3%) organsm disturbance (2%) menstrual disorder (1%)

Body as whole - headache ( 25% ), asthenia (12%), infection (6%) , chills ( 3%), chest pain ( 2%), trauma ( 2%,) weight loss( 1%) , yawn ( 3% )

Dermatologic - sweating ( 12 % ), rash ( 3%), pruritus( 1% )

GI - nausea (37%), constipation( 15%) , anorexia ( 11%), diarrhea ( 8% ), vomiting ( 6% ), dyspepsia ( 5%), flatulance( 3% )

None reported

Special precautions:

Anxiety and insomnia, appetite weight changes, activation of mania/hypomania,treatment of cardiac patients, drug abuse dependent Monitoring- No specific laboratory tests recommended.

Long term use- the effectiveness in long term use (ie > 4 to 6 weeks) has not been evaluated. Therefore periodically re-evaluate the long term usefulness of the drug for the individual patient

Anxiety and insomnia- anxiety ,nervousness and insomnia were commonly reported for venlafaxine- treated patients

Appetite/eight changes- anorexia was more commonly reported for venalfaxine treated than placebo. A dose-dependent weight loss was often noted in patients for several weeks. Howevr, discontinuation for weight loss associated with venlafaxine was uncommon

Mania/hypomania- hypomania occred in patients treated with venlafaxine. As with all antidepressants, use venlafaxine cautiously in patients with a history of mania

Seizures- were reported in venlafaxine treated patients .Use venlafaxine cautiously in patients who develop seizures.

Suicide- the possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial therapy. Write prescribtions for the smallest quantity of tablets consistent with good management in order to reduce the risk of overdose,

Concomittant illness- caution is adviced in administering venlafaxine in patients with diseases or conditions that could affect hemodynamic responses or metabolism.

Cardiac patients- venlafaxine has not been evaluated in patients with a recent history of myocardial infarction or unstable heart disease.

Drug abuse and dependence- there was no indication of drug-seeking behaviour in the clinical trials. Carefully evaluate patients for history of drug abuse and follow such patients closely, observe them forsigns of misuse or abuse of venlafaxine

Warnings- MAO inhibitors- in patients receiving antidepressants with pharmacological properties similar to venlafaxine in combination with an MAOI, there have reports of serious fatal,reactions. Based on the half-life of venlafaxine allow at least 7 days after stopping venlafaxine before starting an MAOI. Sustained hypertension- venlafaxine treatment is associated with sustained increaes in blood pressure. For patients who experience a sustained increae in blood pressure consider either reduction or discontinuation.

Renal/Hepatic function impairment- use with caution in patients with renal impairment. A lower dose may be necessary.

Elderly- no overal differences in efectiveness safety or respoinse were observed between elderly and younger patients

Pregnancy- use during pregnancy only if clearly needed.

Lactation- excercise caution while administering to a nursing woman.

Children- safety and efficacy in patients < 18 years old have not been established.

Approved by FDA on December 28,1993

Indications:

Depression

Dosage:

Starting dose

75mg/day administered in 2 or 3 divided doses, taken with food. Dose may be increased to 150mg/day, if needed further increased dose upto 225mg/day. While increasing dose , make increments of 75mg/day at intervals of more than 4 days.

Maximum dose 375mg/day generally in 3 divided doses. For depression 75mg daily administered two or three divided doses with food. May be increased after several weeks to 150mg daily.

Overdosage

Symptoms Somnolence was most commonly reported

Treatment

1. Treatment should consist of general measures employed in the management of overdosage with any antidepressant

2. Ensure an adequate airway,oxygenation, and ventilation.

3. Monitoring of cardiac rhythm and vital signs is recommended

4. General supportive and symptomatic measures are also recommended.

5. Consider use of activated charcoal, induction of emesis or gastric lavage.

6. Due to the large volume of distribution of venalafaxine forced diuresis. dialysis, hemoperfusion and exchange transfusion are unlikely of benefit.

7. No specific antidotes are known.

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 (April 2003)

Generalised Anxiety Disorder (GAD)

Comparative effectiveness of various Interventions

Definition

1. Excessive worry and tension on most days or atleast for six months

2. With increased motor tension - fatiguability, trembling, restlessness, muscle tension

3. With automatic hyperactivity shortness of breath, rapid heart rate, dry mouth, cold hands and dizziness, but not panic attacks

4. With increased vigilance and scanning- feeling keyed up, increased startling, impaired concentration

Beneficial

1. Cognitive therapy

Likely to be beneficial

1. Buspirone

2. Certain antidepressants ( paroxetine, imipramine,trazodone, venlafaxine )

Trade-off between benefits and harms

1. Benzidiapines

Unknown effectiveness

1. Anti-psychotivc drugs

2. Beta-blockers

KEY BLOCKERS

1. A systemic review of randomised clinical trials (RCTs) has found cognitive therapy with behavoiural interventions is more effective than no treatment, anxiety management training alone, or non-directive therapy. No adverse effects were noticed.

2. One systermic review of randomised clinical trials (RCTs) has found that benzodiapines are clinically effective and rapid treatment for generalised anxiety disorder. One RCT found no significant difference in the effects of slow release alprozolam and bromozepam.

3. RCTs have found that buspirone is effective in GAD. Slower onset compared with benzodiapines is counter balanced by few side efects

4. RCTs have found that imipramine, trazodone, venlafaxine and paroxetine are effective treatments for GAD. One trial has found that paraxetine was more effective than benzodiapines. There is a significant risk of side effects with these drugs.

5. It was found that beta-blockers had not been adequately evaluated in GAD.

VENLAFAXINE- ANTIDEPRESSANT 

1. Caution patients about operating hazards, including automobiles, until they are reasonably certain that velafaxine 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 reaction to Venlafaxine. Also tell your doctor if you are allergic to any other substances, such as foods, preservatives or dyes.

3.Pregnancy - Studies have not been done in pregnant women. Before taking this medicine, make sure your doctor knows if you are pregnant or if you may become pregnant

4.Breast feeding- It is not known whether Venlafaxine passes into breast milk. Mothers who aretaking this medicine and who wish to breast feed should discuss with the doctor

5. Children- Studies on this medicine have been done only in adult patients and there is no specific information comparing use of venlafaxine in children with use in other age groups

6. Elderly- Studies done on elderly people did not cause different side efects or problems in older people than it did in younger adults.

7. Other medicines - Let your doctor know what other medicines you are taking, so that he can advice you accordingly.

8.MAOI - may cause confusion, agitation, restlesness, stomach or intestinal symptoms, sudden high body temperature, extremely high blood pressure, and severe convulsions. upto 14 days should be allowed between stopping treament and starting treatment with the other.

9. Other medical problems - Tell your doctor if you have any other medical problems especially - Drug abuse or dependence - because venlafaxine is a new medicine, it is known ifit could become habit forming, causing mental or physical dependence Heart disease or High or low blood pressure - venlafaxine may make these conditions worse Kidney disease or Liver disease - higher blood levels of venlafaxine may occur, increasing the chance of side effects Seizures- risk of seizures increased

10. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

11. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

12. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Pharmacology:

Venlafaxine is chemically unrelated to tricyclic, tetracyclic or other available antidepressants. Venlafaxine and its active metabolite are potent inhibitors of neuronal serotonin and norepineephrine reuptake and weak inhibitors of dopamine uptake. They do not possess monoamine oxidase inhibitor activity.

Pharmacokinetics:

Venlafaxine is well absorbed and extensively metabolised in th eliver. About 87% of the active dose is recovered in the urine within 48 hours.

Not significant

Pregnancy:

Use during pregnancy only if clearly required. Lactation: Excercise caution while administering to a nursing woman.

Children:

Safety and efficacy in patients less than 18 years old have not been estabilshed