ADVANCED THERAPY OF DEPRESSION

SWATI SURESH BHARATI(B.Pharm)

CONTENT•Introduction Of Depression•Classification•Mechanism Of Action•Marketed Drug•Advance Therapy Of Management Of Depression •Conclusion

Introduction to depression

DEFINITION“An affective disorder characterized by loss of interest orPleasure in almost all a person’s usual activities orPast times.”It may be an unipolar or biopolar disorder in whichcycles of mood swings from mania to depression occursover time.

SYMPTOMS:• Sadness, Despair, Guilt• Decrease in energy• Decrease in sex drive• Insomnia and fatigue• Thoughts of death and suicide• Mental slowing, lack of concentration

Mostly Depression Found In....???

Classification of depression1.Reversible inhibitors of MAO-A (RIMAs) Eg. Moclobemide, clogyline2.Tricyclic antidepressants (TCAs)a. Noradrenaline and 5-HT reuptake inhibitors Eg. Imipramine , amitriptylineb. Predominantly noradrenaline reuptake inhibitors Eg. Desipramine, nortriptyline3.Selective serotonin reuptake inhibitors (SSRIs) Eg. Fluoxetine, citalopram, escitalopram4.Serotonin and noradrenaline reuptake

inhibitors(SNRIs) Eg. Duloxetine5.Atypical antidepressants Eg. Trazodone, amineptine, tianeptine

Mechanism Of Action

Mechanisms of action

Mostly used.....

•The most widely prescribed medications for depression are drugs in the SSRI category, such as fluoxetine (Prozac), citalopram (Celexa), and sertraline (Zoloft)

•These drugs correct chemical imbalances by increasing the level of serotonin, a neurotransmitter that affects mood, to the brain

•SSRIs are now considered to be frontline pharmaceutical treatment for depression.

Drug Used In DepressionSr.no Name of drug Class Dose and dosage

form1 CYMBALTA

(Duloxetine HCl)SNRI (2004)

Tab, Cap:20-60 mg/day

2 LEXAPRO(escitalopram oxalate)

SSRIs(2002)

Tablets:5-20mg oral solution:5mg/5mL

3 ZOLOFT(sertraline HCl)

SSRIs(1991)

Tab ,film coated:50-200mg/day

4 PROZAC(fluoxetine HCl)

SSRIs(1986)

Tab:10-90mg/dayOral:20mg/5mL

5 CELEXA(Citalopram HBr)

SSRIs(1998)

Tab:20-60mg/day

6 Xanax(alprazolam)

Benzodiazepines(1981)

Tab:0.25-4mg/day

TRIPLE REUPTAKE INHIBITORS New class of psychoactive medications which inhibit neuronal reuptake of 5-HT,NE and dopamine. These TRI’S may also have efficacy in obesity, addiction and pain syndromes TRI’s exert their activity by treating more symptoms of MD and/or attenuate some side effects observed for the traditional antidepressants

EXAMPLE:BICIFADINE (approved tri)

St. Johns WortSt. John’s Wort or Hypericum perforatum is a plant which grows in the wild and is widely prescribed for depression in EuropeMechanism of action : Partially understood but is similar to that of SSRI’s • Clinical trials carried out have found it as effective as a commonly prescribed antidepressant • Combining antidepressants and SSRI’s leads to serotonin syndrome • It can induce metabolism of drugs like: Cyclosporine, Digoxin, Warfarin, Birth control pills ,Indinavir etc.

Ketamine

A DRUG WHICH ACTS THROUGH NON-MONOAMINERGIC SYSTEM

AGOMELATINE: •In depression, sleep is greatly disturbed.•Melatonin produced by the pineal gland is an important regulator of circadian rhythms/sleep cycle Chemically melatonin is N-acetyl-5-methoxytryptamine. •Agomelatine(naphthalene derivative of melatonin) acts on both the melatonergic(MT1 and MT2)and 5HT2C receptors co-localized in the SCN of the brain.

According to a recent study:

"The rate of treatment response following first-line treatment with SSRIs is moderate, varying from 40 to 60 percent; remission rates vary from 30 to 45 percent. Up to one third of persons taking antidepressant medications will develop recurrent symptoms of depression while on therapy."

Treatment for depression

Advance therapy of depression

• AUGMENTATION THERAPY:

• PSYCHOLOGICAL THERAPY:

-Supportive Therapy-Interpersonal Therapy-Cognitive Behavioral Therapy

(CBT):a. Cognitive Therapyb. Behavioral Therapy-Dialectical Behavior Therapy-Family Focused Therapy -Psychodynamic Therapy -Light Therapy

-Transcranial Magnetic Stimulation (TMS)therapy

• CAM(COMPLEMENTARY AND ALTERNATIVE MEDICINE):

-Mediation For Stress Managements (Yoga)

-Dietary Guidelines, Exercise, Nutritional Supplements

-Expressive Or Creative Therapy

-Animal Assisted Therapy-Play Therapy

New drug in depression

REXULTI(BREXPIPRAZOLE)(2015)

BRINTELLIX(VORTIOXETINE)(2013)

FETZIMA(LEVOMILNACIPRAN)(2013)

VIIBRYD (VILAZODONE HYDROCHLORIDE)(2011)

OLEPTRO (TRAZODONE HYDROCHLORIDE) (2010)

Rexulti(brexpiprazole)

Rexulti (brexpiprazole) is an atypical antipsychotic.Rexulti is specifically indicated for the adjunctive treatment of major depressive disorder and the treatment of schizophrenia.Rexulti is supplied as a tablet for oral administration

MOA

Rexulti (brexpiprazole) is an atypical antipsychotic. The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. 

Brintellix(vortioxetine)

Brintellix (vortioxetine) is a serotonin modulator and stimulator. It belongs to a psychotropic class of chemical compunds known as bis-aryl-sulphanyl amines.Brintellix is specifically indicated for Major Depressive Disorder.Brintellix is supplied as a tablet for oral administration. The recommended starting dose is 10 mg administered orally once daily without regard to meals. The dose should then be increased to 20 mg/day, as tolerated.

.

MOA

The mechanism of the antidepressant effect of vortioxetine is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through inhibition of the reuptake of serotonin (5-HT). It also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism.

Fetzima(levomilnacipran)

fetzima (levomilnacipran) is an extended release selective norepinephrine and serotonin reuptake inhibitor.Fetzima is specifically indicated for the treatment of Major Depressive Disorder.Fetzima is supplied as a capsule for oral administration. The recommended dose is 40 mg to 120 mg once daily with or without food. Initiate dose at 20 mg once daily for 2 days and then increase to 40 mg once daily. The dose should be increased in increments of 40 mg at intervals of 2 or more days. The maximum recommended dose is 120 mg once daily. The capsules should be swallowed whole.

MOAFetzima (levomilnacipran) is an extended release selective norepinephrine and serotonin reuptake inhibitor. The exact mechanism of the antidepressant action of levomilnacipran is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of reuptake at serotonin and norepinephrine transporters. Non-clinical studies have shown that levomilnacipran is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI).

VIIBRYD (VILAZODONE HYDROCHLORIDE)

Viibryd (vilazodone hydrochloride) is a selective serotonin reuptake inhibitor and a 5HT1A receptor partial agonist. The mechanism of the antidepressant effect of vilazodone is not fully understoodViibryd is specifically indicated for the treatment of major depressive disorder.The recommended initial dose of Viibryd is 40 mg once daily. Treatment should be titrated, starting with an initial dose of 10 mg once daily for 7 days, followed by 20 mg once daily for an additional 7 days, and then an increase to 40 mg once daily.

MOAViibryd (vilazodone hydrochloride) is a selective serotonin reuptake inhibitor and a 5HT1A receptor partial agonist. The mechanism of the antidepressant effect of vilazodone is not fully understood but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown.

Oleptro (trazodone hydrochloride)

Oleptro (trazodone hydrochloride) is an anti-depressant that acts as a dual serotonin agonist and serotonin reuptake inhibitor. Although the exact mechanism of action is unknown, trazodone appears to increase serotonin activity via three mechanisms: the activation of neuronal serotonin receptors; the inhibition at the neuronal serotonin receptors of the feedback system which regulates the action of serotonin; and the inhibition of the re-uptake of serotonin.Oleptro is specifically indicated for the treatment of major depressive disorder in adults.Oleptro is supplied as an extended-release tablet designed for oral administration. The recommended initial dose of Oleptro is 150 mg once daily. The dose may be increased by 75 mg/day every three days. The maximum daily dose should not exceed 375 mg.

MOA

It is an anti-depressant that acts as a dual serotonin agonist and serotonin reuptake inhibitor. Although the exact mechanism of action is unknown, trazodone appears to increase serotonin activity via three mechanisms: the activation of neuronal serotonin receptors; the inhibition at the neuronal serotonin receptors of the feedback system which regulates the action of serotonin; and the inhibition of the re-uptake of serotonin.

AUGMENTATION THERAPY:

AUGMENTATION THERAPY In case of inadequate response to conventional antidepressant therapy Augmentation therapy is includes combining of an augmenting agents along with the conventional antidepressant Augmentation therapy, can avoid patients from unnecessary switching between antidepressants which may jeopardize the remission rates and even aggravate existing side effects augmentation: the action or process of making or becoming greater in size or amount

Medication Data supporting efficacy as augmentation agent

Lithium Positive RCTs with TCAs, limited RCTs with SSRIs, comparable to T

Thyroid Hormones

Positive RCTs with TCAs, limited RCTs with SSRIs, comparable to lithium

Bupropion Open –lable trials comparable to buspirone ,no RCTsMitazapine Multiple Positive RCTs and comparable to MAOIPinolol Negative RCTsSex Hormones Mixed data most convincing for testosterone in men

with low or borderine- low testosterone levelsAripiprazole 3 large Positive RCTs Ofanzapine 2 Positive RCTs And 3 Negative RCTOmega -3 Fatty Acids

Increases small positive RCT

Creatine Increases positive RCT in womanSAMe Increases small positive RCT RCT- randomized controlled trial

T-tridothyronine

PSYCHOLOGICAL THERAPY

Psychotherapy, or "talk therapy", is a way to treat people with a mental disorder by helping them understand their illness.

Supportive Therapy•Long term therapy with various attempt by a therapist by any practical means whatever to help patients deal with their emotional distress and problems in living. •Most mature people lose their ability to provide support from within when they are excessively scared or in pain.

ROLE OF THERAPIST IN SUPPORTIVE THERAPY

• Educate him to the unwritten but crucial rules that govern all social interaction. • Encourages his patient to expand his/her interests in the world by making friends, or by going to school or to work. • Encourage participation in sports or hobbies

Interpersonal Therapy Based on the idea that improving communication patterns The ways people relate to others will effectively treat depression. IPT helps identify how a person interacts with other people. Help patients adopt regular daily routines and sleep/wake cycles, stick with medication treatment, and improve relationships. Research has found that when ipsrt is combined with medication, it is an effective 

Cognitive Behavioral Therapy (CBT):

•At the heart of cognitive therapy is the idea that our thoughts can affect our emotions.• Cognitive behavioural therapy (CBT) developed out of behaviour modification, cognitive therapy, and rational emotive behaviour therapy, and combines cognitive and behavioural techniques. •Cognitive therapies for suicide prevention, and schizophrenia and other psychopathologies.

Dialectical Behavior TherapyDBT is a combination of Cognitive Behavior Therapy and Eastern meditative practices.

Family Focused Therapy

Light Therapy

Transcranial Magnetic Stimulation (TMS)therapy

CAM(COMPLEMENTARY AND ALTERNATIVE MEDICINE)

Mediation For Stress Managements (Yoga)Dietary Guidelines, Exercise, Nutritional Supplements

Expressive Or Creative TherapyAnimal Assisted Therapy

Play Therapy

Thank you