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Mental Health Nursing: Pharmacology-Antidepressants C. Calzolari 2016 Antidepressants Are used to treat mild to severe depression. They are also used for “Off label” use. Many people have to work with HCP and try different antidepressants until they find the right one for them. Most people need to take an antidepressant for 6 weeks before they feel the full effect. Antidepressants Some side effects subside after a few weeks, others only go away after the medication is stopped. Most antidepressants must be tapered off. Instruct patients not to stop suddenly. Any patient who experiences mania s/s, esp. when starting on SSRIs, should contact MD. May need to be evaluated for bipolar disorder. Warning The caregivers of children taking SSRIs should monitor them for depression that is getting worse and thoughts about suicide. The caregiver or medical consenter should immediately talk to the doctor if this happens. Antidepressants Certain brain chemicals, called neurotransmitters, are associated with depression: Serotonin Norepinephrine Dopamine How do antidepressants work? Most antidepressants inhibit the reabsorption (reuptake) of neurotransmitters into nerve cells, and block nerve cell receptors. This provides more neurotransmitters to the brain, which boosts mood. They may also lower the nerve cell’s sensitivity to glutamate, an amino acid, that excites and overwhelms brain areas associated with anxiety and depression. Classifications of Antidepressants Monoamine oxidase inhibitors (MAOIs) Tricyclic antidepressants Tetracyclic antidepressants Selective serotonin reuptake inhibitors (SSRIs) Serotonin & norepinepherine reuptake inhibitors (SNRIs) Norepinepherine & dopamine reuptake inhibitors (NDRIs) Monoamine oxidase inhibitors (MAOIs) MAOIs are the first antidepressants to be used, dating back to the 1950s. How do they work? – they prevent the enzyme monoamine oxidase from metabolizing the 3 neurotransmitters mentioned before. As a result, more of the neurotransmitters are available to the brain. Monoamine oxidase inhibitors (MAOIs) These MAOIs are approved by the FDA for treatment of depression: Nardil (phenelzine) Parnate (tranylcypromine) Marplan (isocarboxazid) Emsam (selegiline) transdermal patch Monoamine oxidase inhibitors (MAOIs) Side effects: Drowsiness, constipation, nausea, diarrhea, GI upset, fatigue, dry mouth, dizziness, hypotension, orthostatic hypotension, decreased urinary output, decreased sexual function, sleep disturbances, muscle twitching, weight gain, blurred vision, headache, restlessness, trembling, increased diaphoresis. Monoamine oxidase inhibitors (MAOIs) Safety concerns: high risk MAOIs are usually reserved for persons whose depression doesn’t improve with other medications. MAOIs can cause dangerous interactions with certain foods, beverages and medications. Monoamine oxidase inhibitors (MAOIs) Foods/beverages that contain high levels of tyramine are prohibited: cheeses, yeast, pickled foods, chocolates, certain meats and fruits, alcohol (even alcohol free beer). What can happen? High increase in blood pressure Drug to drug interactions: other antidepressants, antihypertensives, diabetes medicine, certain pain medications such as Ultram & Demerol, OTC decongestants, herbal weight loss products and St. John’s Wort. Tricyclic Antidepressants They inhibit the reabsorption (reuptake) of mainly serotonin & norepinepherine and less so, dopamine. These are some of the earliest antidepressants. Many side effects. Tricyclic Antidepressants Tricyclics approved by FDA for treatment of depression: Elavil (amitriptyline) Asendin (amoxapine) Norpramin (desipramine) Sinequan (doxepin) Tofranil (imipramine) Vivactil (protriptyline) Surmontil (trimipramine) Pamelor (nortriptyline) Tricyclic Antidepressants Side effects: orthostatic hypotension, drowsiness, dizziness, impaired sexual function, disorientation, headache, sensitivity to sunlight, weight gain, nausea, weakness. Anticholinergic effects: dry mouth, blurred vision, constipation, urinary retention, tachycardia Tricyclic Antidepressants Precautions: with DM, seizure HX or thyroid problems, kidney disease, elderly. Drug reactions with CNS depressants, anticholinergics, MAOIs. Contraindications: narrow-angle glaucoma, BPH, certain heart diseases. Tetracyclic Antidepressants They work a little differently. They work by preventing neurotransmitters from binding with certain nerve cell (alpha-2) receptors. This indirectly increases the levels of serotonin and norepinepherine in the brain. FDA aprroved tetracyclics: Remeron (mirtazapine) Side effects: drowsiness, weight gain, dry mouth, dizziness, thirst, aches, constipation, increased cholesterol. Safety concerns: rare s.e. – agranulocytosis. MD to be notified in case of fever, sore throat, flu- like symptoms. Selective serotonin reuptake inhibitors (SSRIs) Most commonly prescribed antidepressants. The first drug in this class was Prozac, in 1987. SSRIs affect serotonin levels in the brain. FDA approved SSRIs: Celexa (citalopram) Lexapro (escitalopram) Prozac (fluoxetine) Paxil (paroxetine) Zoloft (sertraline) Selective serotonin reuptake inhibitors (SSRIs) Side effects: nausea, sexual dysfunction, dry mouth, headache, diarrhea, nervousness, rash, agitation, restlessness, diaphoresis, weight gain, drowsiness, insomnia. Safety concerns: a rare but potentially lifethreatening s.e. – serotonin syndrome. Pregnancy – will discuss later in lecture Use of ASA, NSAIDS or Coumadin with SSRIs increases risk of GIB. Serotonin & Norepinepherine reuptake inhibitors (SNRIs) Increase serotonin & norepinepherine levels in the brain. FDA approved SNRIs: Cymbalta (duloxetine) Effexor (venlafaxine) Serotonin & Norepinepherine reuptake inhibitors (SNRIs) Side effects: nausea, vomiting, dizziness, insomnia, sleepiness, abnormal dreams, constipation, diaphoresis, dry mouth, yawning, tremor, flatus, anxiety, agitation, abnormal vision, headache, sexual dysfunction. Safety concerns: with high doses of Effexor, hypertension may occur. Also raises cholesterol. Avoid all SNRIs with glaucoma. Use of ASA, NSAIDS, Coumadin may increase risk of GIB. Norepinepherine & dopamine reuptake inhibitors (NDRIs) They increase the levels of both norepinepherine & dopamine by inhibiting their reabsorption into cells. FDA approved NDRIs for depression: Wellbutrin (bupropion) Norepinepherine & dopamine reuptake inhibitors (NDRIs) Side effects: loss of appetite, weight loss, headache, dry mouth, rash, diaphoresis, nervousness, stomach pain, agitation, constipation, anxiety, dizziness, trouble sleeping, muscle pain, nausea, fast HR, sore throat, frequent urination. Safety concerns: may increase BP, contraindicated with seizure HX ,TBI, eating disorders. Can cause liver problems. Patient should not smoke. Misc. Antidpressant Trazadone is a trazolopyridine antidepressant. Because of its sleep inducing effects, it is more likely prescribed as a sleep aide. Safety concern: can cause priapism. Related Topics Antidepressant Discontinuation Syndrome Serotonin Syndrome How to manage side effects Suicide with the use of antidepressants Use with children, teens and the elderly Off Label use Safety in pregnancy New research Antidepressant Discontinuation Syndrome Occurs in appx. 20% of patients after abrupt discontinuation of an antidepressant drug that was taken for at least 6 weeks. S/S: flu-like symptoms, insomnia, nausea, headache, nightmares, ataxia, dizziness, blurred vision, numbness, anxiety, agitation, psychosis with MAOIs. Antidepressant Discontinuation Syndrome Patients at Risk: Patients may be tempted to d/c medications after they begin to feel better. Pregnant women. How to prevent? Tapering of the antidepressants is recommended How to treat this syndrome? It generally runs its course within 1-2 weeks. TX for trycyclics may require anticholinergic drugs. Serotonin Syndrome Characterized by very high levels of serotonin. Can occur when combinations of drugs that affect serotonin are used. S/S: Agitation, confusion, hallucinations, loss of coordination, fast HR, changes in BP, fever, profuse diaphoresis, hyperreflexes, nausea, vomiting, diarrhea, seizures, coma. Serotonin Syndrome Drugs that may cause Serotonin Syndrome are: SSRIs SNRIs NDRIs MAOIs Pain medications – such as fentanyl, Demerol, Ultram Anti-nausea medications – Zofran, Reglan Migraine medications – Imitrex, Axert, etc. OTC cough/cold medicines Street drugs – Ectasy, LSD Herbal supplements – ginseng, St. John’s Wort Lithium Serotonin Syndrome Treatment: Stop these drugs. May require observation in hospital for monitoring. Should resolve in 24 hours. Severe s/s will require more extensive TX in hospital: muscle relaxants, serotonin-production blocking agents, drugs that control heart rate and BP. How to Manage Common Side Effects Most people taking antidepressants will experience at least one side effect. Many side effects subside after a few weeks. Some remain as long as the drug is taken. Instruct your patient to notify MD if any side effects become problematic. The most common side effects are: constipation or diarrhea, drowsiness, dizziness, dry mouth, headache, nausea, sexual dysfunction, tremors, sleep disturbances, weight gain. GI Disturbances Constipation: increase po intake, high fiber diet, more fruits and vegetables. Nausea: discuss with MD and/or pharmacist. Timing of administration may help. Anti-nausea medications should be avoided. Why? Usually subsides within 30 days. Diarrhea: may subside. If a problem, MD may switch drug. BRAT diet if necessary. Other Side Effects Dizziness: instruct patient to change positions slowly, especially upon arising. Drowsiness: timing of administration may help. Night time administration if OK with MD. May subside over time. Insomnia: once again, timing of administration may help. Give early in day. Sometimes, Trazadone is ordered for night to induce sleep. Tremors: depending on severity, MD may have to switch medication. Other Side Effects Dry mouth: may subside with time. Hard candies or gum may help. Frequent oral care. Headache: usually subsides with time. Weight gain: some drugs cause more weight gain than others. Wellbutrin may actually cause weight loss. Sexual dysfunction: major cause of noncompliance. Wellbutrin is least likely to cause this side effect. Prozac, Paxil & Zoloft have highest rate of sexual s.e. Risk of Suicide In some instances, antidepressants have been associated with worsening symptoms of depression or suicidal thoughts, especially in children, teens, and young adults. Close monitoring at the beginning of treatment and with any changes in dosages is recommended. Use With Children, Teens and the Elderly Children: not many antidepressants have been approved for use with children. Only Prozac is approved by the FDA for major depression. Therefore, all other antidepressants are prescribed “Off Label”. Teens and Young Adults: must be monitored closely because of high risk of suicide for this age group combined with increased risk associated with the administration of antidepressants. See handout. Elderly: FDA recommends smallest effective total dose . Certain antidepressants may be contraindicated with dementia. Also, many elderly patients are on multiple medications, which increases risk of adverse drug interactions. Also, medications may be metabolized more slowly due to the aging process. Off Label Use What does that mean? Doctors prescribe a medication to treat a disease that is different than the disease(s) studied by federal regulators. Or they may prescribe a drug that has not been studied by the FDA in certain populations, such as children. In other words, off label use is not approved by the FDA. Many drugs used for off label use are antidepressants and antipsychotics. Examples: Zoloft is approved for depression but is prescribed off label for bipolar disorder. Implications? Safety and efficacy has not been formally studied. Insurance companies may not cover for off label prescriptions. So … why do doctors prescribe this way? Safety with Pregnancy There is a low risk of birth defects with certain antidepressants. Many SSRIs, Nardil and Parnate should be avoided as per the Mayo Clinic. If a woman is being treated for depression, discussions with treating MD should be discussed well in advance of pregnancy. New Research Serotonin is one of several neurotransmitters that brain cells use to communicate with each other. Abnormalities are believed to be involved with depression, bipolar disease, anxiety disorder, autism and schizophrenia. Scientists are researching the chain of molecular events that are involved with mental illnesses. They are finding that certain genes and enzymes are involved as well. They are experimenting on mice to block the enzyme and to manipulate the affecting gene.