Download Depression and Newer Antidepressants

Depression and Newer
Antidepressants
Ashraf B. Abdel-Naim
Professor of Pharmacology and Toxicology
Faculty of Pharmacy
King Abdul Aziz University
Jeddah, KSA
‫بسم هللا الرحمن الرحيم‬
‫َّ ُ َّ َ ْ َ َ ْ َ ُ َ َ‬
‫ِإنا كل ش ي ٍء خلْقَاُ ِِْقَ ٍر‬
‫سورة الْقمر– آية ‪49‬‬
What is a depressive
disorder?
• A depressive disorder is a syndrome that
reflects a sad mood exceeding normal
sadness or grief.
• Depression
symptoms
are
also
characterized by neurovegetative signs
(irregular eating, sleeping, crying spells,
and decreased libido).
Depressive disorders are a huge
public health problem
• Direct and indirect costs
• Depression causes significant problems more
often than do arthritis, hypertension, chronic
lung disease, and diabetes.
• Depression increases the risks for developing
HIV, coronary artery disease, and asthma.
• Depression is frequently under-diagnosed.
• Depression is often under-treated.
Women and depression
• Women are twice as likely to become
depressed as men.
• Postpartum depression
Types of depression
• Major Depression
It is characterized by sad mood that interferes with the ability to
work, sleep, eat, and enjoy once-pleasurable activities.
• Dysthymia
Dysthymia is a less severe type of depression. Chronic symptoms
that do not disable, but prevent the affected person from functioning
at "full steam".
•
Bipolar Disorder (Manic Depression)
It involves cycles of depression and mania . The mood switches are
sometimes dramatic and rapid, but most often they are gradual.
Symptoms of Depression
•
•
•
•
•
•
•
•
•
Persistently sad mood
Feelings of hopelessness, pessimism
Feelings of guilt, worthlessness, helplessness
Loss of interest in hobbies and activities that were once
enjoyed, including sex
Insomnia, or oversleeping
Decreased appetite or overeating
Fatigue, decreased energy
Persistent physical symptoms such as headache,
digestive disorders, and chronic pain
Thoughts of death or suicide
Symptoms of Mania
•
•
•
•
•
•
•
•
•
Inappropriate elation
Inappropriate irritability
Severe insomnia
Grandiose notions
Increased talking speed and/or volume
Disconnected and racing thoughts
Markedly increased energy
Poor judgment
Inappropriate social behavior
What are the causes of depression?
• Genetic (especially with bipolar disorder)
• Stressful environment
Biochemical Basis of Depression
• The depressive disorders appear to be
associated with low brain serotonin and
norepinephrine.
Drug Treatment of Depression
I. Monoamine oxidase inhibitors
(MAOIs)
• Phenelzine, Tanylcypromine (non-selective)
• Clorgyline, Moclobemide (MAO-A-selective)
• Cheese Reaction
II. Tricyclic Antidepressants
• Imipramine, desipramine, amitriptyline,
nortroptyline, amoxapine, doxipin
•
•
•
•
Anticholinergic activity
Sexual dysfunction
Cardiac toxicity
Orthostatic hypotension
III. Selective serotonin
reuptake inhibitors
(SSRIs)
• Fluoxetine (Prozac), fluvoxamine (Luvox),
paroxetine (Paxil), sertraline (Zoloft),
citalopram (Cipram)
• Little or no anticholinergic, alpha or histamine
blocking activity.
• Decreased sexual desire (decreased libido),
delayed orgasm
• Serotonergic syndrome
IV. Serotonin/norepinephrine
reuptake inhibitors
• Venlafaxine (Effexor), duloxetine (Ariclaim)
• Venlafaxine is considered an SNRI, a serotonin
and norepinephrine reuptake inhibitor.
• It has particularly robust effects.
• These drugs (SNRI) seem to be very promising,
especially for the more severe and chronic cases
of depression.
V. Atypical antidepressants
• Bupropion
• Mirtazapine
• Nefazodone & Trazodone
• Tianeptine (Stablon)
Bupropion
• It acts as norepinephrine and dopamine
reuptake inhibitor
• Bupropion has been found to be effective
as a smoking cessation aid.
Mirtazapine (Remeron)
• It is a tetracyclic compound.
• It enhances serotonin and norepinephrine.
• It is devoid of anticholinerigic, antiadrenergic or
serotonin-related side effects
• Mirtazapine is given at bedtime and is often
prescribed for people who have trouble falling
asleep.
Nefazodone and Trazodone
• These drugs are weak inhibitors of serotonin reuptake.
• Their therapeutic benefit is related to their ability
to block 5-HT1 presynaptic auto receptors and,
thereby, increase serotonin release.
• Both agents are sedating, probably because of
their potent H1-blocking activity.
Tianeptine (Stablon)
• Selective serotonin reuptake enhancer!
• Tianeptine acts to prevent and even
reverse stress-induced neural damage,
promoting both neuronal survival and
synaptic plasticity.
VI. Mood Stabillizers
• Lithium
Other Mood-Stabilizing Drugs
• Anticonvulsants: Valproate, Carbamazepine,
Gabapentin, and Lamotrigine
• Antipsychotics: Quetiapine, Risperidone
Non-Pharmacological Treatment
of Depression (Psychotherapy)
• Talking therapies
• Interpersonal and cognitive/behavioral
therapies
• Psychodynamic therapies
• Electroconvulsive therapy
Natural Products as Antidepressant
• Saint John's wort
(Hypericum
pefforatum)
• Most probably, it
acts as a SSRI.
Self-help
•
•
•
•
Do not set difficult goals for yourself.
Break large tasks into small ones.
Do not expect too much from yourself too soon.
Try to be with other people, which is usually
better than being alone.
• Participate in activities that may make you feel
better.
• Do not make major life decisions, such as
changing jobs or getting married without
consulting others who know you well.
• Do not accept your negative thinking.
Guidelines
• In severe recurrent depressive illnesses, an
antidepressant (or ECT) along with
psychotherapy are required for the best
outcome.
• If a person suffers one major depressive
episode, he or she has a 50% chance of a
second episode.
• If the individual suffers two major depressive
episodes, the chance of a third episode is 75 to
80%.
• If the person suffers three episodes, the
likelihood of a fourth episode is 90 to 95%.
• After a second and certainly after a third
episode, a patient should remain on a
maintenance dosage of the medication.
• SSRIs are usually used initially because of
their lower severity of side effects.
• Side effects of SSRI s can be minimized by
starting tat low doses and gradually increasing
the doses till full therapeutic effects.
• If SSRIs fail, antidepressants with dual action
are to be tried.
• Other options include bupropion, which has
action on dopamine.
• Sometimes a combination of antidepressants
from different classes may be used.
• For MAOIs, take care of the cheese reaction.
• Alcoholic liquors reduce the effectiveness of
antidepressants and should be avoided.
• Benzodiazepines are not antidepressants but
they are occasionally prescribed with
antidepressants for a brief period of anxiety.
However, they should not be taken alone for
depressive disorder.