Antidepressants PDF

Antidepressants 1  Introduction Overview depression – The symptoms of are feelings of sadness and hopelessness – inability to experience pleasure in usual activities, changes in sleep patterns and appetite, loss of energy, and suicidal thoughts....

Antidepressants 1  Introduction Overview depression – The symptoms of are feelings of sadness and hopelessness – inability to experience pleasure in usual activities, changes in sleep patterns and appetite, loss of energy, and suicidal thoughts. Mania – Is characterized by the opposite behavior: enthusiasm, anger, rapid thought and speech patterns, extreme self-confidence, and impaired judgment. 2 3 4  Selective Serotonin Reuptake Inhibitors The selective serotonin reuptake inhibitors (SSRIs) – are a group of antidepressant drugs – specifically inhibit serotonin reuptake, – have 300- to 3000-fold greater selectivity for the serotonin transporter 5 6  Cont.. – SSRIs are relatively safe in overdose, – Have largely replaced TCAs and monoamine oxidase inhibitors (MAOIs) as the drugs of choice in treating depression. Fluoxetine, citalopram, escitalopram, fluvoxamine, paroxetine, and sertraline – Antidepressants, including SSRIs, typically take at least 2 weeks to produce improvement in mood, and maximum benefit may require up to 12 weeks or more 7 8  Cont.. Therapeutic uses The primary indication for SSRIs is depression. A number of other psychiatric disorders also respond favorably to SSRIs, including – obsessive–compulsive disorder, – panic disorder, – generalized anxiety disorder, – posttraumatic stress disorder, social anxiety disorder, – premenstrual dysphoric disorder, and bulimia nervosa (only fluoxetine is approved for bulimia) 9  Cont.. Adverse effects – headache, sweating, anxiety and agitation, – gastrointestinal (GI) effects (nausea, vomiting, and diarrhea), – weakness and fatigue, – sexual dysfunction, changes in weight, – sleep disturbances (insomnia and somnolence), 10 11  Cont.. Discontinuation syndrome – SSRIs have the potential to cause a discontinuation syndrome after their abrupt withdrawal, – Fluoxetine has the lowest risk of causing an SSRI discontinuation syndrome due to its longer half-life and active metabolite. – Possible signs and symptoms of SSRI discontinuation syndrome include headache, malaise and flu-like symptoms, agitation and irritability, nervousness, and changes in sleep pattern. 12 Serotonin-Norepinephrine Reuptake Inhibitors – Venlafaxine, desvenlafaxine, levomilnacipran, and duloxetine – inhibit the reuptake of both serotonin and norepinephrine and, thus, are termed SNRIs. – Depression is often accompanied by chronic pain, such as backache and muscle aches, for which SSRIs are relatively ineffective. – This pain is, in part, modulated by serotonin and norepinephrine pathways in the central nervous system 13  Cont.. – With dual inhibition of serotonin and norepinephrine reuptake, both the SNRIs and the TCAs may be effective in relieving pain. – These agents are also used in the treatment of pain syndromes, such as diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and low back pain. – The SNRIs, unlike the TCAs, have little activity at α- adrenergic, muscarinic, or histamine receptors and, have fewer receptor mediated adverse effects than the TCAs. 14 15  Cont.. Atypical Antidepressants – The atypical antidepressants are a mixed group of agents that have actions at several different sites. – This group includes bupropion, mirtazapine, nefazodone trazodone vilazodone and vortioxetine 16  Cont.. – Bupropion is a weak dopamine and norepinephrine reuptake inhibitor that is used to alleviate the symptoms of depression. useful for decreasing cravings and attenuating withdrawal symptoms of nicotine in patients trying to quit smoking. Side effects may include dry mouth, sweating, nervousness, tremor, and a dose dependent increased risk for seizures 17  Tricyclic Antidepressants The TCAs inhibit norepinephrine and serotonin reuptake into the presynaptic neuron Include, – amitriptyline, – clomipramine, doxepin, – nortriptyline AND – Imipramine 18  Cont.. Blocking of receptors – TCAs also block serotonergic, α-adrenergic, histaminic, and muscarinic receptors. – It is not known if any of these actions produce the therapeutic benefit of the TCAs. – However, actions at these receptors are likely responsible for many of their adverse effects. 19  Cont.. Actions – The TCAs improve mood, in 50% to 70% of individuals with major depression. – The onset of the mood elevation is slow, requiring 2 weeks or longer. – Patient response can be used to adjust dosage. – Tapering of these agents is recommended to minimize discontinuation syndromes and cholinergic rebound effects 20  Cont.. Therapeutic uses – The TCAs are effective in treating moderate to severe depression. – Some patients with panic disorder also respond to TCAs. – Imipramine is used as an alternative to desmopressin (enuresis alarms) in the treatment of bed-wetting in children. – 21  Cont.. – The TCAs, particularly amitriptyline, have been used to help prevent migraine headache and treat chronic pain syndromes (for example, neuropathic pain) in a number of conditions for which the cause of pain is unclear. Low doses of TCAs, especially doxepin, can be used to treat insomnia. 22  Cont.. Adverse effects – Blockade of muscarinic receptors leads to blurred vision, xerostomia, urinary retention, sinus tachycardia, constipation, and aggravation of angle-closure glaucoma. – These agents affect cardiac conduction similar to quinidine and may precipitate life- threatening arrhythmias in an overdose situation. – The TCAs also block α-adrenergic receptors, causing orthostatic hypotension, dizziness, and reflex tachycardia 23  Cont.. – All antidepressants, including TCAs, should be used with caution in patients with bipolar disorder, even during their depressed state, – may cause a switch to manic behavior. – The TCAs have a narrow therapeutic index (for example, five- to six-fold the maximal daily dose of imipramine can be lethal). – Depressed patients who are suicidal should be given only limited quantities of these drugs and be monitored closely. 24  Monoamine Oxidase Inhibitors Monoamine oxidase (MAO) – is a mitochondrial enzyme found in nerve and other tissues, such as the gut and liver. – In the neuron, MAO functions as a “safety valve” to oxidatively deaminate and inactivate any excess neurotransmitters (for example, norepinephrine, dopamine, and serotonin) that may leak out of synaptic vesicles when the neuron is at rest. 25  Cont.. The MAOIs – may irreversibly or reversibly inactivate the enzyme, – permitting neurotransmitters to escape degradation and, therefore, to accumulate within the presynaptic neuron and leak into the synaptic space 26  Cont.. The four MAOIs currently available for the treatment of depression include – phenelzine, tranylcypromine, isocarboxazid and selegiline. – [Note: Selegiline is also used for the treatment of Parkinson disease. – It is the only antidepressant available in a transdermal delivery system. 27 28  Cont.. Therapeutic uses – The MAOIs are indicated for depressed patients who are unresponsive or intolerant of other antidepressants. – Because of their risk for drug–drug and drug–food interactions, the MAOIs are considered last-line agents in many treatment settings. 29  Cont.. Adverse effects – MAOIs can result severe and often unpredictable side effects. – For example, tyramine, which is contained in foods, such as aged cheeses and meats, liver, pickled or smoked fish, and red wines, is normally inactivated by MAO in the gut. – Individuals receiving a MAOI are unable to degrade tyramine obtained from the diet. 30  Cont.. – Tyramine causes the release of large amounts of stored catecholamines from nerve terminals, – Results in a hypertensive crisis, with signs and symptoms such as occipital headache, stiff neck, tachycardia, nausea, hypertension, cardiac arrhythmias, seizures, and, possibly, stroke. – Patients must, therefore, be educated to avoid tyramine- containing foods. – Other possible adverse effects of treatment with MAOIs include drowsiness, orthostatic hypotension, blurred vision, dry mouth, and constipation 31  Treatment of Mania and Bipolar Disorder – The treatment of bipolar disorder has increased in recent years due to increased recognition of the disorder – There is increase in the number of available medications for the treatment of mania. 32  Cont.. Lithium – Lithium salts are used acutely and prophylactically for managing bipolar patients. – Lithium is effective in treating 60% to 80% of patients exhibiting mania and hypomania. – Although many cellular processes are altered by treatment with lithium, the mode of action is unknown. 33  Cont.. – The therapeutic index of lithium is extremely low, and lithium can be toxic. – Common adverse effects may include headache, dry mouth, polydipsia, polyuria, polyphagia, GI distress, fine hand tremor, dizziness, fatigue, dermatologic reactions, and sedation. Adverse effects due to higher plasma levels may indicate toxicity and include ataxia, slurred speech, coarse tremors, confusion, and convulsions. Thyroid function may be decreased and should be monitored. 34 Lithium S/E 35 Lithium S/E 36 37 38  Cont.. Other drugs – Several antiepileptic drugs, including carbamazepine, valproic acid, and lamotrigine are approved as mood stabilizers for bipolar disorder. – Other agents that may improve manic symptoms include the older (chlorpromazine and haloperidol) and newer antipsychotics. – 39  Cont.. The atypical antipsychotics are also used for the management of mania. – risperidone, – olanzapine, ziprasidone, – aripiprazole, – asenapine, – cariprazine, and – quetiapine 40 Thank You For Your Attention 41