Depression and Newer Antidepressants

Ashraf B. Abdel-NaimProfessor of Pharmacology and Toxicology

Faculty of Pharmacy

King Abdul Aziz University

Jeddah, KSA

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د�ر� ن�اه ب�ق� ل�ق� خ�

بسم الله الرحمن الرحيم

49سورة القمر – آية

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 re-uptake.

• 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.

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