Depression and Newer Antidepressants Ashraf B. Abdel-Naim Professor of Pharmacology and Toxicology Faculty of Pharmacy King Abdul Aziz University Jeddah, KSA
إِنَّا كُلَّ شَيْءٍ خَلَقْنَاهُ بِقَدَرٍ بسم الله الرحمن الرحيم سورة القمر – 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.
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.