DEPRESSION AND ANXIETY-SSRI AS FIRST CHOICE

1. Effective approach
in treatment of
anxiety and
depression
The road to recovery

4. Mechanism of anxiety
• Overactivation of brain
neurotransmission and
neuronal firing
(glutamate/calcium influx)
• Underinhibition of brain
neurotransmission and
neuronal firing (GABA)
• Both

5. • Generalized anxiety disorder
• Obsessive-compulsive disorder
• Panic disorder
• Post-traumatic stress disorder
• Social phobia (or social anxiety disorder)
Anxiety disorders - Types

7. Definition
• Depression is a common
mental (mood) disorder,
characterized by sadness, loss
of interest or pleasure,
feelings of guilt or low self-
worth, disturbed sleep or
appetite, feelings of tiredness,
and poor concentration.

8. Epidemiology
• Chances of developing a depressive illness are estimated to be 1 in 5 for
women and 1 in 10 for men
• The WHO estimated that within 20 years, recurrent depressive disorder will
be the second most serious cause of morbidity and burden of disease in the
world.
• Depression affects approximately 350 million people worldwide; constituting
a major portion of mental health disorders.
• According to the World Mental Health Survey, approximately 6% people aged
18 years and above have had an episode of depression in the previous year.
• Lifetime prevalence rates of depression range from 8 to 12% in most countries

9. Symptoms of depression
 Persistently sad, anxious, or "empty"
mood.
 Feelings of hopelessness.
 Feelings of guilt, worthlessness,
helplessness.
 Loss of interest (anhedonia) or pleasure
in hobbies and activities that were once
enjoyed.
 Insomnia, early-morning awakening, or
oversleeping.

10. Symptoms of depression
 Decreased appetite and/or weight loss, or
overeating & weight gain.
 Fatigue, decreased energy, being "slowed
down."
 Thoughts of death or suicide, suicide attempts.
 Restlessness, irritability.
 Difficulty concentrating, remembering, making
decisions.
 Persistent physical symptoms that do not
respond to treatment, such as headaches,
digestive disorders, and chronic pain.

11. Mechanism of depression
The monoamine hypothesis
states that depression is
caused by a deficiency of
monoamines, particularly
noradrenaline and serotonin.
(NA & 5-HT)

14. Positive and negatives of anti-
anxiety drug options

15. SSRI- AS DRUG OF CHOICE
• It is considered as first choice for depression, anxiety and
co-morbid depression associated with anxiety.
• Block presynaptic serotinin reuptake(5-HT), which
increases serotinin levels in the synapse
• SSRIs have little effect on the NE or dopamine
transporters and a low affinity for the histaminic,
muscarinic/cholinergic, and alpha receptors.
• Hence adverse effects are less as compared to TCAs.

17. SSRI
• Fluoxetine
• Fluvoxamine
• Paroxetine
• Sertaline
• Citalopram
• Escitalopram

18. PAROXETINE
 Paroxetine is US FDA approved
SSRI
 No dependence or addiction
potential
 Lowers intraplatelet serotonin
levels
 Inhibits platelet plug formation
 Does not activate coagulation
 Paroxetine normalizes heart rate
variability
Paroxetine
Paroxetine blocks the uptake
of serotonin, thus increasing
serotonin concentration at
synaptic cleft

19. Indication
• Major Depressive Episodes
• Obsessive Compulsive Disorder
• Panic Disorder with and without agoraphobia
• Social Anxiety Disorder/Social phobia
• Generalised Anxiety Disorder
• Post-traumatic Stress Disorder

20. Dosage recommendation of normal
paroxetine tablet
• Administered once daily in the morning with food

21. dosage recommendation of paroxetine controlled
release tablet

22. Adverse effects
• Akathisia- restlessness and psychomotor agitation (such as an inability to
sit or stand)
• Serotonin syndrome/Neurolept malignant syndrome (characterised by
clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic
instability with possible rapid fluctuations of vital signs, mental status
changes including confusion, irritability, extreme agitation progressing to
delirium and coma)
• Withdrawal symptoms (Dizziness, sensory disturbances, sleep
disturbances, anxiety, nausea, tremor, confusion, sweating, headache,
diarrhoea, palpitations. Emotional instability, irritability, and visual
disturbances)

23. Warning & precautions
 Paroxetine should not be used for the treatment of
children and adolescents (7-17 years) as controlled
clinical trials have found paroxetine to be associated with
increased risk for suicidal behaviour and hostility.
 Increased plasma concentrations of paroxetine occur in
patients with severe renal impairment (creatinine
clearance less than 30 ml/min) or in those with hepatic
impairment. Therefore, dosage should be restricted to
the lower end of the dosage range.

24. Warning & precautions
At least two week should elapse between discontinuation of paroxetine
and initiation of therapy with any MAOI.
• As with all antidepressants, paroxetine should be used with caution in
patients with a history of mania. Paroxetine should be discontinued in any
patient entering a manic phase.
• Teratogenic Effects: Pregnancy Category D Epidemiological studies
have shown that infants exposed to paroxetine in the first trimester of
pregnancy have an increased risk of congenital malformations, particularly
cardiovascular malformations.
• Paroxetine is secreted in human milk, and caution should be exercised
when paroxetine hydrochloride is administered to a nursing woman.

25. ESCITALOPRAM
• US FDA approved since 2002
• S- enantiomer of citalopram.
• Enantiomer: non-superimposable mirror images of one another. This
property is known as “chirality”
• Escitalopram is a selective serotonin reuptake inhibitor (SSRI) indicated for:
 Acute and Maintenance Treatment of Major Depressive Disorder (MDD) in
adults and adolescents aged 12 -17 years
 Acute Treatment of Generalized Anxiety Disorder (GAD) in adults

26. DOSAGE RECOMMENDATION

27. WARNING & PRECAUTIONS
• Clinical Worsening/Suicide Risk: Monitor for clinical worsening,
suicidality and unusual change in behaviour, especially, during the
initial few months of therapy or at times of dose changes
• Serotonin syndrome
• Seizures: Prescribe with care in patients with a history of seizure
• Activation of Mania/Hypomania: Use cautiously in patients with
a history of mania
• Hyponatremia: Can occur in association with SIADH

28. WARNING & PRECAUTIONS
• Abnormal Bleeding: Use caution in concomitant use with
NSAIDs, aspirin, warfarin or other drugs that affect
coagulation
• Pregnancy category C: Use only if the potential benefit
justifies the potential risk to the fetus
• Nursing Mothers: Caution should be exercised when
administered to a nursing woman

29. RATIONALITY OF L-METHYLFOLATE
COMBINATION WITH ESCITALOPRAM
• Depression is linked with folate deficiency and that patients with insufficient folate are
less likely to respond to treatment and more likely to experience a relapse.
• One theory of depression is that the brain is not developing enough neurotransmitters.
This may be due to insufficient amounts of L-methylfolate in the brain.
• L-methylfolate is needed to regulate serotonin, norepinephrine and dopamine
production.
• Without enough L-methylfolate, it may be difficult to produce enough
neurotransmitters for antidepressants to work fully.
• L-methylfolate, is indicated for the distinct nutritional requirements of
individuals who have suboptimal L-methylfolate levels in the CSF, plasma, and/or
red blood cells and have major depressive disorder, with particular emphasis as
adjunctive support for patients taking antidepressant medications.

31. RATIONALITY OF COMBINATION
• ESCITALOPRAM being SSRI blocks reuptake of neurotransmitters,
while L-methylfolate augments the production of more
neurotransmitters
• Clinical trials suggest that L-methylfolate augments
antidepressant effect of SSRI/SNRI.
• Combination is cost-effective option than second generation
antidepressants.
To conclude, Adjunctive L-methylfolate at 7.5 mg/day may constitute an
effective, safe, and relatively well tolerated treatment strategy for patients
with major depressive disorder who have a partial response or no response
to SSRIs. Hence it is rationale to combine it with ESCITALOPRAM.

32. desvenlafexine
• Atypical antidepressant.
• It is serotonin and norepinephrine reuptake inhibitor (SNRI)
• Desvenlafaxine : major active metabolite of venlafaxine
• Desvenlafaxine lacks significant affinity for numerous receptors,
including muscarinic-cholinergic, H1 -histaminergic, or α -
adrenergic receptors in vitro.
• Desvenlafaxine also lacks MAO inhibitory activity.
• Efficacy demonstrated against vasomotor symptoms of
menopause, physical symptoms associated with depression
(somatic pain, fatigue, irritability etc.)

33. Desvenlafaxine vs. venlafaxine
• No dose titration required; starting dose is the target dose;
once-daily dosing.
• Efficacy demonstrated against painful symptoms associated
with depression.
• Minimal hepatic metabolism (no concerns about CYP 2D6
slow and extensive metabolizers).
• Very small effect on pulse and BP at 50 mg/day.
• Efficacy demonstrated against vasomotor symptoms of
menopause

34. Dosage and administration
• Recommended dose: 50 mg once daily with or without food
• Discontinuation: Reduce dose gradually whenever possible
• Moderate renal impairment: Maximum dose 50 mg per day
• Severe renal impairment and end-stage renal disease:
Maximum dose 50 mg every other day.
• Moderate to severe hepatic impairment: Maximum dose 100
mg per day.

35. Adverse reactions
• Nausea,
• Dizziness,
• Insomnia,
• Hyperhidrosis,
• Constipation,
• Somnolence,
• Decreased appetite,
• Anxiety, and specific male sexual function disorders

36. Warning & precautions
• Hyponatremia:Can occur in association with SIADH
• Interstitial Lung Disease and Eosinophilic Pneumonia
• Pregnancy category C: use only if the potential benefits justify the
potential risks to the fetus.
• Nursing Mothers: Discontinue drug or nursing taking into
consideration importance of drug to mother
• Geriatric Use: There is an increased incidence of orthostatic
hypotension in desvenlafaxine treated patients ≥ 65 years

37. Anxiety and Depression
• Depression often accompanies anxiety
disorders and, when it does, it needs to be
treated as well
• Symptoms of depression include feelings of
sadness, hopelessness, changes in appetite or
sleep, low energy, and difficulty
concentrating.
• Most people with depression can be
effectively treated with antidepressant
medications, psychotherapy, or a
combination of both.

38. Comorbid depression with anxiety
• It is recommended that anxiety symptoms should be taken into account when
assessing the most appropriate antidepressant agent for treating someone with
depression, to optimize treatment outcome and recovery rate
• Escitalopram/paroxetine/desvenlafexine is extensively prescribed
medication for major depression.
• Clonazepam is a high-potency, long-acting benzodiazepine with anxiolytic
property.
• Clonazepam's long half-life of 20 to 80 hours render this compound especially
promising for augmentation therapy in major depression, because interdose
fluctuation in mood state is less.
• Hence it is rationale to combine it with SSRI for comorbid depression with
anxiety.