Anti depressant drugs Flashcards
what is depression
• Depression is characterized by intense feeling of sadness,
hopelessness, lack of motivation, despair, inability to experience
pleasure, changes in sleep and appetite, loss of energy, & suicidal
thoughts.
• Among emotional symptoms: Anxiety (in 90% of cases),
pessimistic outlook, and feeling of worthlessness.
• Among physical symptoms: Headache & palpitations, increased
sensitivity to painful stimuli.
• Among cognitive symptoms: Poor memory for recent events,
indecisiveness, psychotic features (auditory hallucination,
delusions).
what are the uses of antidepressants
1) Depression
2) Anxiety Disorders (PTSD, OCD, social anxiety disorder
and panic disorder)
3) Pain Disorders
4) Premenstrual Dysphoric Disorder: A combination of
emotional, physical, psychological, and mood disturbances
that occur after ovulation and normally end with the onset of
the menstrual flow.
5) Eating Disorders
• Bulimia nervosa: An eating disorder which is characterized
by intake of large amounts of food followed by self-induced
vomiting.
• Anorexia nervosa: Anorexia is a disorder in which reduced
food intake, and the person has a morbid fear of gaining
weight.
what are the uses of antidepressants
1) Depression
2) Anxiety Disorders (PTSD, OCD, social anxiety disorder
and panic disorder)
3) Pain Disorders
4) Premenstrual Dysphoric Disorder: A combination of
emotional, physical, psychological, and mood disturbances
that occur after ovulation and normally end with the onset of
the menstrual flow.
5) Eating Disorders
• Bulimia nervosa: An eating disorder which is characterized
by intake of large amounts of food followed by self-induced
vomiting.
• Anorexia nervosa: Anorexia is a disorder in which reduced
food intake, and the person has a morbid fear of gaining
weight.
what are the MOAs of anti depressants
• Biogenic amine theory: decreased brain levels of the
monoamines neurotransmitters norepinephrine (NE),
serotonin (5-HT), and dopamine (DA) may cause
depression
• Treatment of depression is centered on ↑:
• Serotonergic
• Noradrenergic
• &/or Dopaminergic neurotransmission.
what are SSRIs
• MOA: block reuptake of serotonin.
• Replaced TCAs & MAOIs as 1st
-line therapy because less A/E & safer in overdose.
• Fluoxetine, citalopram, escitalopram, fluvoxamine, paroxetine, sertraline.
• Typically take at least 2 weeks to produce significant improvement in mood, and
maximum benefit may require up to 12 weeks or more.
• Patients that do not respond to one antidepressant may respond to another.
• Approximately 80% or more will respond to at least one antidepressant drug.
• SSRIs have little blocking activity at muscarinic, α-adrenergic, and histaminic H1
receptors.
what are SSRIs therapeutic uses
Major depression
-Obsessive compulsive disorder
-Panic disorder
-Premenstrual dysphoric disorder
-Generalized anxiety disorder,
-Posttraumatic stress disorder,
-Social anxiety disorder, and
-Bulimia nervosa (only fluoxetine is approved for bulimia).
what are the pharmacokinetics of SSRIs
• All of the SSRIs are well absorbed after oral administration.
• Food has little effect on absorption .
• The majority of SSRIs have plasma half-lives that range between 16
and 36 hours.
• Metabolism by CYP450–dependent enzymes.
• t1/2 of fluoxetine is long and is metabolized to an active metabolite.
• Fluoxetine is available as sustained-release preparation to be given
once a week: Prozac Weekly®.
• Fluoxetine & paroxetine are potent inhibitors of CYP2D6, which is
responsible for the elimination of TCAs, antipsychotic drugs, some
antiarrhythmic and β-adrenergic antagonist drugs.
• Dosages of the SSRIs should be reduced in patients with hepatic
impairment.
what are the side effects of SSRIs
a) Sleep disturbances: insomnia, somnolence.
• Paroxetine & fluvoxamine are sedating and they may be useful in patients who
have difficulty sleeping.
• Fluoxetine & sertraline are activating for patients who are fatigued or
complaining of excessive somnolence.
b) Sexual dysfunction: which may include loss of libido, delayed ejaculation and
anorgasmia, is common with the SSRIs.
One option for managing SSRI-induced sexual dysfunction is to change the
antidepressant to one with fewer sexual side effects, such as bupropion or
mirtazapine. Alternatively, the dose of the drug may be reduced.
- Weakness, headache, anxiety (combined with a benzodiazepine for the first few
weeks to decrease anxiety).
- All antidepressants, but mostly SSRIs, can cause hyponatremia especially in the
elderly and patients who are volume depleted or taking diuretics.
Suicidality and antidepressant drugs: antidepressants increased the
risk of suicidal thinking and behavior (suicidality) in children,
adolescents, and young adults in short-term studies of major
depressive disorder (MDD) and other psychiatric disorders.
what are the side effects of SSRIs
a) Sleep disturbances: insomnia, somnolence.
• Paroxetine & fluvoxamine are sedating and they may be useful in patients who
have difficulty sleeping.
• Fluoxetine & sertraline are activating for patients who are fatigued or
complaining of excessive somnolence.
b) Sexual dysfunction: which may include loss of libido, delayed ejaculation and
anorgasmia, is common with the SSRIs.
One option for managing SSRI-induced sexual dysfunction is to change the
antidepressant to one with fewer sexual side effects, such as bupropion or
mirtazapine. Alternatively, the dose of the drug may be reduced.
- Weakness, headache, anxiety (combined with a benzodiazepine for the first few
weeks to decrease anxiety).
- All antidepressants, but mostly SSRIs, can cause hyponatremia especially in the
elderly and patients who are volume depleted or taking diuretics.
Suicidality and antidepressant drugs: antidepressants increased the
risk of suicidal thinking and behavior (suicidality) in children,
adolescents, and young adults in short-term studies of major
depressive disorder (MDD) and other psychiatric disorders.
what happens when you overdose on SSRI
Overdose with SSRIs does not usually cause cardiac arrhythmias, with the
exception of citalopram, which may cause QT prolongation.
• Seizures are a possibility.
• All SSRIs have the potential to cause serotonin syndrome, especially when used
in the presence of a MAOI or other highly serotonergic drug.
• Serotonin syndrome: shivering, diaphoresis, muscle rigidity, tachycardia,
hypertension, agitation, delirium, shock, (hyperthermia seizures, renal
failure).
• SSRIs should be spaced by weeks from MAOIs.
how do we discontinue SSRIS (discontinuation syndrome)
• All of the SSRIs have the potential to cause a discontinuation syndrome after
their abrupt withdrawal, particularly the agents with shorter half-lives and
inactive metabolites. Fluoxetine has the lowest risk of causing an SSRI
discontinuation syndrome due to its longer half-life and active metabolite.
• SSRIs should be D/C gradually to avoid discontinuation symptoms that include
headache, flu-like symptoms, agitation, nervousness, and changes in sleep
pattern.
For antidepressants in general:
1) Not effective for mild forms of depression
2) ↓ Dose of the antidepressant over (8 weeks - 6 months) to avoid
W/S if patient has been taking the drug for >8 weeks.
3) Effect is not prompt. It may take weeks before effect is seen. This
should be explained for the patient.
4) Weeks should be allowed as a wash-out period after cessation of
one antidepressant & the initiation of another.
5) No major teratogenic effects have been identified with the SSRIs
or TCAs. However, fluoxetine may cause premature birth & ↓ fetal
growth rate.
SSRIs are FDA pregnancy category C.
6) All antidepressants should be used with caution in patients with
bipolar disorder, even during their depressed state, because they
may cause a switch to manic behavior.
what are SNRIs
• Venlafaxine, desvenlafaxine, and duloxetine.
• Can be effective in a patient who didn’t respond to SSRIs
• Also effective in relieving chronic pain (like backache and
muscle aches) that often accompanies depression and is
nonresponsive to SSRIs.
• Also for neuropathy of diabetes, postherpetic neuralgia,
fibromyalgia, and low back pain.
• The SNRIs have little activity at α-adrenergic, muscarinic, or
histamine receptors and, thus, have fewer of these receptor-
mediated adverse effects than the TCAs.
• The SNRIs may precipitate a discontinuation syndrome if
treatment is abruptly stopped.
what are SNRIs
• Venlafaxine, desvenlafaxine, and duloxetine.
• Can be effective in a patient who didn’t respond to SSRIs
• Also effective in relieving chronic pain (like backache and
muscle aches) that often accompanies depression and is
nonresponsive to SSRIs.
• Also for neuropathy of diabetes, postherpetic neuralgia,
fibromyalgia, and low back pain.
• The SNRIs have little activity at α-adrenergic, muscarinic, or
histamine receptors and, thus, have fewer of these receptor-
mediated adverse effects than the TCAs.
• The SNRIs may precipitate a discontinuation syndrome if
treatment is abruptly stopped.
what are Venlafaxine and desvenlafaxine:
Venlafaxine is a potent inhibitor of
serotonin reuptake and, at medium to higher doses, is an inhibitor of
norepinephrine reuptake (and serotonin)..
• Desvenlafaxine is the active, demethylated metabolite of venlafaxine.
• A/E: insomnia, sedation, constipation & hypertension (high dose). Fatal in
overdose.
• D/C syndrome.
