Selective serotonin reuptake inhibitors include

- Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

Refer- Fluoxetine
 

Interacting drugs - summary                                                             
       
                         
  Cimetidine + SSRIs paroxetidine 
  cimetidine increased steady-state paroxetine concn.   
                   
  Cyproheptidine + Fluoxetine 
  Pharmacologic effects of flouoxetine may be decreased

  Dextromethhorphan + Fluoxetine
  Hallucinations occured during concurrent use

  MAO inhibitors + SSRIs
  Serious sometimes fatal reaction  occurred

  Phenobarbital + SSRIs Paroxetine 
   Phenobarbital decreased AUC and half-life of paroxetine

  Phenytoin +  SSRIs Paroxetine 
  Phenytoin reduced AUC and half life of paroxetine
  SSRIs Paroxetine + Phenytoin 
   also paroxetine reduced AUC and half life of phenytoin

  Smoking + SSRIs  Fluvoxamine 
  smokers had 25% increase in metabolism of fluvoxamine

 L-tryptophan  + SSRIs Fluoxetine, Fluvoxamine, Paroxetine    
Concurrent use with fluoxetine produce central toxicity  symptoms
 
 
  SSRIs  +  Alcohol  
    concurrent use not recommended in depressed patients

 SSRIs   Fluoxetine, fluvoxamine   + Tricylic Antidepress
 Plasma TCA  levels increased 
  
SSRIs , fluvoxamine,   +  Antihistamine- non sedat 
Plasma  level of astemazole,terfenadine increased    

SSRIs , Fluvoaxamine, sertaline  + Benzodizepine 
clearance of benzodiazepine decreased           

SSRIs Fluvoxamine  + Betablockers   
propranol plasma level increased

SSRIs Fluoxetine +  Buspirone 
Effects of buspirone  decreased

SSRIs  Fluvoxetine, Fuvoxamine   + Carbamazepine
Serum carbamazepine level increased    

SSRIs  Fluvoxamine +  Clozapine
Eevated serum clozapine level

SSRIs Fluvoxamine  +  Diltiazem
Bradycardia has occurred

SSRIs  Paroxetine +    Digoxin 
Paroxetine decreased AUC  of digoxin

SSRIs Fluvoxamine, Setraline,     + Lithium
Serum levels increased by fluoxetine,  setraline did not affect lithium levels

Lithium   + SSRIs Fluvoxamine 
Lithium enhance fluvoxamine effects

SSRIs  Fluvoxamine  +  Methadone
Increased methadone level

SSRIs  Paroxetine  +   Procyclidine 
Paroxetine increased AUC  level of procylidine

SSRIs Fluvoxamine  + Theophylline 
Clearance of theophylline  decreased, reduce dosage
 
SSRIs Setraline  +  Tolbutamide  
Decreased clearance of tolbutamide

SSRIs Fluoxamine      + warfarin 
Increased bleeding with unaltered  PT

Adverse Reactions-

FLUOXETINE-

BODY AS A WHOLE -

Headache, Asthenia, Abdominal pain,  Infection Viral/bact , Pain ,                                            Fever ,Chest pain ,   Influzenza/Flu synd, 

CARDIOVASCULAR -

Palpitations , Vasodilation

  CNS -     

 Insomnia, 13%Nervousness 15%, Anxiety,9%Dizziness 6%,Tremor 8% 
   Drowsiness 11% , Fatigue 4%  

  GI     

 Nausea 21%, Vomiting 2% Diarrhea 12% Dyspepsia 6% Dry mouth 9%
    Anorexia 8% Constipation 4%  Flatulance 1%

   RESPIRATORY 

   Upper respiratory infectn  7% , Yawn 1%

  SKIN  

   Sweating 8% Rash 3% Pruritus 2%

  SPECIAL SENSES   

  Blurred vision  3% Taste perversion 2%

  GU      

  Menstruation painful 2%Urinary frequency 2%

Severe renal failure, lactation, hypersens, comcomittant MAOIs

Special precautions:

Unstable epilepsy, liver failure, renal impairment, cardiac disease, diabetes, pregnancy. Anxiety nervousness and insomnia- occured in 2.6% of patients treated with an SSRI. These effects led to discontinuation of drug therapy im 1.1% to 5.3%.

Altered appetite and weight- significant weight loss especially in underweight depressed patients has occurred

Activation of mania/hypomania- ocured infrequently about 0.1% to 2.2% of patients taking SSRIs Seizures- have occured with fluoxetine, fluvoxamine.paroxetine and sertaline.

Usewith caution in patients with a history of seizures

Suicide- the possibility of a suicide attempt is inherent in depression and may persist until significantly remission occurs.

Write prescribtions for the smallest quantity of tablets or capsules to reduce the risk of overdose.

Concomittant ilness- clinical experiences is very limited. Use withcaution in patients withdiseases or conditions that could metabolism or hemodynamic response.

Electoconvulsive therapy- )ECT)- there are no clinical studies establishingthe benefit of the combined use of ECT and SSRI.

Hyponatremia- the majority of occurances have been

Diabetes- the dosage of insulin and sulfonylurea may need to be adjusted when fluoxetine is started or discontinued

Uricosuric acid- the clinical significance of weak uricosuric acid is unknown and there have been no reports of acute failure with sertaline.

Drug abuse and dependence- Before staring SSRI carefully evaluate patients for history of drug abuse and follow such patients closely,observing them for signs of misue or abuse.

Hazardous tasks- patients should be instructed to observe caution while driving or performing tasks requiring alertness,cordination and physical dexterity.

Warnings-

Long term use- Periodically reevaluate the SSRI used for extended periods to determin long term usefulness of the drug for the patient.

MAO inhibitors- periodically reevaluate te SSRI used for extended periods to determine long-term usefulness of the drug for the individual patient.

Renal function impairment- reduce initial dose of paroxetine in patients with severe renal impairment, upward titration if necessary should be increased at intervals

Hepatic function impairment- reduce initial dose of paroxetine in patients with severe renal impairment upward titration if necessary should be increased at intervals.

Fertility impairment- a decrease in fertility was seen with sertraline in one or two rats at a dose of 80mg/kg ( 20 timesthe maximum human dose.)

Pregnancy- There are no adequate and well controlled studies in pregnant women

Lactation- excercise caution when SSRIs are administered to a nursing woman

Children- safety and efficacy in children < 18 years have not been established

Approved by (DCI) Drug Controller  GENERAL -  India  For Marketing                                                                                   (Ref- IDMA Publication)

Indications:

Depression

Dosage

: Initial - 20mg/day in the morning considering dose increase after several weeks if no clinical improvement is noticed.

Administer more than 20mg/day on a twice daily schedule. (Morning and noon). Do not exceed 80mg/day.

Overdosage- Symptoms

Fluoxetine- nausea and vomiting were prominent in overdose involving higher fluoxetine doses.

Other symptoms include agitation, restlessness,hypomania, and other sense of CNS excitation.

Fluvoxamine- common symptoms include drowsiness, vomiting, diarrhea, and dizziness,other signs include coma, tachycardia, bradycardia, hypotension, ECG abnormalities, liver function abnormalities and convulsions

Paroxetine- signs and symptoms of overdose include nausea, vomiting,drowsiness,sinus tachycardia and dilated pupils.

Sertaline- no specific therapy required

Treatment

1. There are no specific antidotes.

2. Establish and maintain an airway,ensure adequate oxygenation and ventilation.

3. Activated charcoal which may be used with sorbitol, may be as or more efective than emesis or lavage

4. Monitor cardiac and vital signs along with general symptomatic and supportive measures.

5. SSRI-induced seizures which fail to remit spontaneously may respond to diazepam

6. Due to large volume of distribution of SSRIs forced diuresis dialysis, hemoperfusion and exchange transfusion are likely to be of benefit.

7. Treatment include supportive measures

 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)

                               Premenstrual sydrome

              Comparative effectiveness  of various intreventions

Beneficial

Overall Premenstrual Syndrome Symptoms

1. Prostagalndin inhibitors (e.g. Indomethicin)
2. Selective serotonin Reuptake Inhibitors (e.g. Fluoxetine, Seratinine, Fluvoxamine)

Breast symptoms only

1. Leuteal phase control
2. Bromocriptine

Bloatedness and Swelling

1. Spironolactone/ diuretics

Likely to be beneficial

1. Tobolone
2. Oestrogen
3. Vitamin B-6
4. Evening primrose B-6

Trade-off between Benefits and Harms

1. Danazol
2. Gonodotropin-releasing hormone (GnRH analogues)
3. Non-SSRI antidepressants/ anxiolytics
4. Hysterectomy with/without oophorectomy

Unknown effectiveness
1. Progesterone
2. Progestogens
3. Oral contraceotives
4. Cognitive behaviour treatment
5. Dietary supplements
6. Relaxation treatment
7. Endometrial ablation
8. Laproscipic bilateral oophorectomy

                                    KEY POINTS

1. Trials have found that SSRIs and prostagalndin inhibitors relieve premenstrual symptoms. Antidepressants and
    ovulation suppression with danazol and GnRH analoges are also effective but have significant adverse effects,
    including the masculanising effects of danazol and the menopausal effects of GnHR analogues.

2. There is a limited evidence suggesting that oestrogen, viatmin-B6 , evening Primrose Oil and excercise may also
    be beneficial 

3. Trials have found that bromocriptine is effective for breast symptoms and diuretics are effective for bloatedness
    and swelling. Both can have adverse efects.

4. There is no good evidence to support the use of progesterone or oral contraceptives

5. Few treatments have been adequately validated in trials.  

FLUOXETINE- SELECTIVE SEROTIN REUPTAKE INHIBITORS (SSRI)

1. May cause dizziness. Observe caution while driving or performing tasks requiring alertness, coordination or physical dexterity.

2.Avoid alcohol or other CNS depressants medicines.

3. Concomitant medication- Consult physician or pharmacist before taking concomittant OTC products or prescription drugs

4. Pregnancy or lactation- Notify physician of pregnancy, ofintent to become pregnant or if breast feeding

5. Rash- Notify physician if rash hives develop.

6.Completing course of therapy- While patients may notice improvement in therapy in 1 to 4 weeks, advise patients to continue therapy as directed.

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

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

9.Breast feeding- be sure you have discussed the risk and benefits of this medicine with your doctor.

9.Children- not expected to cause different side effects or problems in children

10. Elderly- not shown to cause different problems in elderly people than in younger adults.

11. Other Medicines -Tell your doctor if you are taking any of the following- Anticoagulants or Digitalis glycosides- higher or lower blood levels of the these medicines or fluoxetine may occur- your doctor may need to change your dose CNS depressants-

11. Other medical problems- presence of other medical problems may affect the use of this medicine- Diabetes - the amount of insulin or oral antidiabettic medicine that you need mat change Kidney disease or Liver disease - higher blood levels of fluoxetine may occurincreasing the chance of side effects. Seizures- the risk of seizures may be increased

12. 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 dose

Pharmacology:

Selective serotonin reuptake inhibitors(SSRIs) are oral antidepressant agents chemically unrelated to the tricyclic,tetracyclic or other available antidepressants.

. The antidepressant action of SSRIs is presumed to be linked to their inhibition of CNS neuronal uptake of serotonin.

Reports not available.

Pregnancy:

There are no adequate and well controlled studies in pregnant women. Use during pregnancy only when needed.

Lactation-

Notify physician of intent to become pregnant or if beastfeeding.Excercise caution when SSRIs are administered to a nursing woman

Children-

Safety and efficacy in children < 18 years have not been established