INTRODUCTION:

Major depressive disorder (MDD) (also known as clinical depression, major depression, unipolar depression, or unipolar disorder; or as recurrent depression in the case of repeated episodes) is a mental disorder characterized by a pervasive and persistent low mood that is accompanied by low self-esteem and by a loss of interest or pleasure in normally enjoyable activities. The precise cause of depression is unknown, but it is believed to result from chemical changes in the brain due to a genetic problem triggered by stressful events, cognitive and environmental factors, or a combination of unknown causes⁽¹⁾.

Type of Major Depressive Disorder:⁽²⁾

· Melancholic depression is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation, excessive weight loss or excessive guilt.

· Atypical depression is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), excessive sleep or sleepiness (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.

· Catatonic depression is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stupor us, and either remains immobile or exhibits purposeless or even bizarre movements.

· Postpartum depression, or mental and behavioral disorders associated with the puerperium, not elsewhere classified, refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression has an incidence rate of 101.5% among new mothers. The DSM-IV mandates that, in order to qualify as postpartum depression, onset occur within one month of delivery.

· Seasonal affective disorder (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.

(Figure -1 Diagram of a chemical synapse between two neurons.)

ARIPIPRAZOLE^(5-7):

· Chemical name: 7-[4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2(1H)-quinolinone.

· Aripiprazole appear as white Crystalline Solid powder. The drug is slightly Soluble in chloroform and ethanol.

· Aripiprazole melts at 134-136 C^(5).

· The pKa value of Aripiprazole is 13.51.⁽⁶⁾

· The molecular formula of Aripiprazole is C₂₃H₂₇C₁₂N₃O₂ . Its molecular weight is 448.39 gm/mol. The structural formula is shown below:

Figure 2: The chemical structure of Aripiprazole.

MECHANISM OF ACTION:

• Aripiprazole is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Aripiprazole is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2) and dopamine Type 2 (D2) receptors. Aripiprazole’s antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia.⁽³⁾

PHARMACOKINETIC⁽⁹⁾:

(Table -1)

Parameter	Observation
Bioavailability	87%
Metabolism	Hepatic
Excretion	Renal

Escitalopram Oxalate^(8-10):

· The chemical name: 1-[3-(Dimethylamino) propyl]-1-(4fluorophenyl)-1,3-dihydro-5-isobenzofuran-carbonitrile oxalate.

· Escitalopram Oxalate is a white crystalline powder that is freely soluble in Methanol.

· Escitalopram Oxalate melts at 146-149°C⁽¹¹⁾

· The pKa value of Escitalopram Oxalate is 9.78⁽¹²⁾

· The molecular formula of Escitalopram Oxalate is C₂₂H₂₃FN₂O₅.Its molecular weight is 414.43 gm /mol. The structural formula is shown below:

Figure 3: The chemical structure of Escitalopram Oxalate.

MECHANISM OF ACTION:

The selective serotonin reuptake inhibitors (SSRIs) are a group of chemically antidepressant drugs that specifically inhibit serotonin reuptake, having 300 to 3000 fold greater selectivity for the serotonin transporter as compared to the nor epinephrine transporter. The SSRIs block the reuptake of serotonin, leading to increased concentrations of the neurotransmitter in the synaptic cleft and, ultimately, to greater postsynaptic neuronal activity.⁽⁴⁾

PHARMACOKINETICS⁽⁸⁾:

(Table -2)

Parameter	Observation
Bioavailability	~80%
Metabolism	Hepatic
Excretion	fecal and Urine

COMBINATION THERAPY OF ARIPIPRAZOLE AND ESCITALOPRAM OXALATE ⁽¹¹⁾

• Aripiprazole is atypical antipsychotic drug and Escitalopram Oxalate is Serotonin reuptake inhibitor drug. Combination of This drugs useful for treatment of Major Depressive Disorders.

• Aripiprazole increase dopamine and serotonin level in intracyneptic cleft and Escitalopram Oxalate increase serotonin level in intracyneptic cleft. So both drug give additive effect in Major depressive Disorders.

CONCLUSION:

By reviewing the all literatures, the combination therapy was found to be effective in treatment of Major Depressive Disorders. This review represents individual pharmacology and pharmacokinetic of Aripiprazole and Escitalopram Oxalate as well as mechanism of action of combination of Aripiprazole and Escitalopram Oxalate in treatment of Major Depressive Disorders. This review will helpful for researcher in future studies and also for development of combined formulation of Aripiprazole and Escitalopram Oxalate as there no formulation is available.

REFERENCES:

1. Major Depressive Disorders: (database available on internet) introduction:https://en.wikipedia.org/wiki/Major_depressive_disorder

2. Charles H brown, “Pharmacotherapy of Major Depressive Disorder.” US Pharm.2011, 36(11), 3-8.

3. Aripiprazole mechanism :information available form drug bank: http://www.drugbank.ca/drugs/DB01238

4. Harvey Richard A and Champe Pamela C, Lippincott Williams & Wilkins Pharmacology; 4th Edn; Walters Kluwer Florida, 2009, pp 142.

5. Aripiprazole Drug info (database available on internet): Drug Bank: Available from : http://www.drugbank.ca/drugs/DB01238

6. Aripiprazole Drug info (database available on internet): lookchem: Available from : http://www.lookchem.com/Aripiprazole/

7. Aripiprazole Drug info (database available on internet): Wikipedia. Available from : https://en.wikipedia.org/wiki/Aripiprazole

8. Escitalopram Oxalate Drug info (database available on internet) http://www.chemicalbook.com/ChemicalProductProperty_EN_CB5712919. html

9. Escitalopram Oxalate Drug info (database available on internet): http://www.scbt.com/datasheet-208365-s-citalopramoxalate.html

10. Escitalopram Oxalate Drug info (database available on internet): Wikipedia. Available from: https://en.wikipedia.org/wiki/Escitalopram.

11. Mattews JD, Siefert C, Dording C and Cenninger JW et al , “An open study of Aripiprazole and Escitalopram for psychotic Major depressive Disorders.” J. clin.Psychopharmacol.2009, (1), 73-76.

Received on 28.03.2016 Accepted on 09.04.2016

Asian J. Res. Pharm. Sci. 2016; 6(2): 113-115

DOI: 10.5958/2231-5659.2016.00016.3

ABSTRACT: