antidepressants€¦ · ssris •selective serotonin reuptake inhibitors (ssris) are frequently...

ANTIDEPRESSANTS

Phr.Volkan KAHRAMAN

DEPRESSION&ANXIETY

• Depression and anxiety disorders are the most common mental illnesses,each affecting in excess of 10-15% of the population at some time in their lives.

SYMPTOMS OF DEPRESSION

• Depression, in general,is classified as major depression(unipolar) or bipolar depression(manic depressive illness).

• Lifetime risk of unipolar depression is 1̴5%.

• Females are affected twice as frequently as males.

• Depressive symptoms can occur secondary to other illnesses such as hypothyroidism,Parkinson’s disease and inflammatory conditions.

• Approximately 10-15% of people with severe depression attempt suicide at some time.

SYMPTOMS OF DEPRESSION

Depressive episodes are characterized by; Depressed or sad mood Pessimistic worry Diminished interest in normal activities Mental slowing and poor concentration Insomnia or increased sleep Significant weight loss or gain due to altered eating and activity

patterns Psychomotor agitation and retardation Feelings of guilt and worthlessness Decreased energy and libido Suicidal ideation,occuring most days for a period of at least 2

weeks.

ANXIETY

• Anxiety is a normal human emotion that serves an adaptive function from a psychobiological perspective.

• Feelings of fear or dread that are unfocused or out of scale with the perceived threat often require treatment.

ANTIDEPRESSANT DRUGS

• Different types of antidepressants work in different ways, but all antidepressants are based on the same principle.

• All antidepressants work by increasing the levels of chemicals called neurotransmitters in the brain.

• Neurotransmitters are ‘messenger chemicals’ that are used to transmit signals between brain cells.

• Some neurotransmitters are also thought to have an important effect on your mood.


• Examples of ‘mood enhancing’ neurotransmitters include:

• Serotonin

• Norepinephrine

• Dopamine

• The role that these neurotransmitters play in the causes of depression (and other mental health conditions) is still poorly understood. However, most experts would say that depression is not simply the result of a chemical imbalance in the brain.

Sites of action of antidepressants. Schematics representing noradrenergic (top) and serotonergic (bottom) nerve terminals. SSRIs, SNRIs, and TCAs increase noradrenergic or serotonergic neurotransmission by blocking the norepinephrine or serotonergic transporter at presynaptic terminals (NET, SERT). MAOIs inhibit the catabolism of norepinephrine and serotonin.


• Depression is a complex condition with many contributing factors.

• While antidepressants can treat the symptoms of depression, they do not necessarily address its causes.

• This is why antidepressants are usually used in combination with therapy to treat moderate to severe depression or other mental health conditions.


• Increasing the levels of neurotransmitters is a gradual process, so most people will need to take antidepressants for two to four weeks before noticing any improvement in their symptoms.

• Some patients may respond to antidepressant treatment sooner than 3-4 weeks;others may require ≥8 weeks for an adequate response.


• Monoamine Oxidase Inhibitors(MAOIs)

• Tricyclic Antidepressants(TCAs)

• Selective Serotonin Reuptake Inhibitors(SSRIs)

• Serotonine-Norepinephrine Reuptake Inhibitors (SNRIs)

• Atypical Antipsychotics

TCAs

• Due to their potential to cause serious side effects, the TCAs generally are not used as first-line drugs for the treatment of depression.

• Because of the role of norepinephrine and serotonin in pain transmission,these drugs are commonly used to treat a variety of pain conditions.

TCAs ADVERSE EFFECTS

• Blurred vision

• Dry mouth

• Tachycardia

• Constipation

• Difficulty urinating

• Orthostatic hypotension and sedation

• Weight gain

TCAs

• Imipramine

• Desipramine

• Amitriptyline

• Doxepin

• Drugs that inhibit CYP2D6, such as SSRIs,may increase plasma exposure of TCAs.

MAOIs

• Monoamine oxidase inhibitors(MAOIs) are chemicals which inhibit the activity of the monoamine oxidase enzyme family.

• They are particularly effective in treating atypical depression.

• They are also used in the treatment of Parkinson's disease and several other disorders.

• Because of potentially lethal dietary and drug interactions, monoamine oxidase inhibitors have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example SSRIs and TCAs) have failed.

MAOIs

• Trancylpromine

• Phenelzine

• Moclobemide

MAOIs ADVERSE EFFECTS

• Hypertensive crisis resulting from food or drug interactions is one of the life-threatening toxicities associated with use of the MAOIs.

• Foods containing tyramine(cheeses,red wines,fava beans) are a contributing factor.

• Blurred vision, dizziness, drowsiness, increased appetite, nausea ,restlessness, shaking or trembling difficulty sleeping

MAOIs INTERACTIONS

• CNS depressants including meperidine and other narcotics,alcohol,anesthetic agents should not be used with MAOIs.

• Meperidine and other opioids in combination with MAOIs also induce the serotonin syndrome.

• SSRIs and SNRIs are contraindicated in patients which use MAOIs.

SSRIs

• Selective serotonin reuptake inhibitors (SSRIs) are frequently used as first-line antidepressants because of their efficacy, tolerability, and general safety in overdose.

• In addition, SSRIs potently treat anxiety, which is often part of depressive syndromes.

SSRIs

• Citalopram

• Escitalopram

• Fluoxetine

• Fluvoxamine

• Paroxetine

• Sertraline

SSRIs

• Citalopram– none

• Escitalopram – none

• Fluoxetine – 2D6 (potent), 2C9, 2C19, 2B6, and 3A4

• Fluvoxamine – 1A2 (potent), 2C19 (potent), 2B6, 2C9, and 3A4

• Paroxetine – 2D6 (potent) and 2B6 (potent)

• Sertraline – 2D6 (potent at doses > 200 mg per day), 2B6, 2C9, 2C19, and 3A4

SSRIs ADVERSE EFFECTS

• SSRIs can prolong the QT interval

• Sexual dysfunction Drowsiness

• Weight gain Insomnia

• Anxiety Dizziness

• Headache Dry mouth

• Blurred vision Nausea

• Rash or itching Tremor

• Constipation Stomach upset

SSRIs ADVERSE EFFECTS

• Serotonin syndrome is a potentially lethal condition caused by overstimulation of central and peripheral serotonin receptors.

• Agitation or restlessness,Confusion,Rapid heart rate and high blood pressure,Dilated pupils,Loss of muscle coordination or twitching muscles,Muscle rigidity,Heavy sweating, Diarrhea, Headache

• Severe serotonin syndrome can be life-threatening. Signs and symptoms include:

• High fever,Seizures,Irregular heartbeat,Unconsciousness

• It typically results from an interaction between multiple medications that increase serotonergic neurotransmission.

CITALOPRAM

• Initial dose is 20 mg.

• Older patients and those sensitive to side effects can be started at a dose of 10 mg.

• The dose range is 20 to 40 mg once per day.

• Clinicians should not prescribe citalopram at doses greater than 40 mg per day.

• Citalopram causes dose-dependent QT interval prolongation that can lead to arrhythmias.

CITALOPRAM

• Recommended a maximum dose of 20 mg per day in patients at risk for increased serum concentrations of citalopram, including patients with;

Hepatic impairment,

Age >60 years,

CYP2C19 variants that slowly metabolize citalopram,

Concomitant medications that inhibit CYP2C19.

ESCITALOPRAM

• Initial dose of 10 mg in the morning or evening.


• The standard dose range is 10 to 20 mg once per day.

FLUOXETINE

• Initial dose of 20 mg in the morning or evening.


• The standard dose range is 20 to 40 mg once per day.

FLUVOXAMINE

• Initial dose of 50 mg at bedtime.


• The standard dose range is 50 to 200 mg per day

PAROXETINE

• Initial dose of 20 mg in the morning.


• The standard dose range is 20 to 40 mg once per day .

SERTRALINE

• Initial dose of 50 mg in the morning.


• The standard dose range is 50 to 150 or 200 mg once per day

antidepressants€¦ · ssris •selective serotonin reuptake inhibitors (ssris) are frequently...

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