PDF Bipolar Disorder Treatment

Treatment Psychopharmacology Treatment for bipolar disorder involves a lifetime regimen of medications—either an antimanic agent called lithium or anticonvulsant medications used as mood stabilizers. This is the only psychiatric disorder in which medications can prevent acute cycles of bipolar behav...

Treatment Psychopharmacology Treatment for bipolar disorder involves a lifetime regimen of medications—either an antimanic agent called lithium or anticonvulsant medications used as mood stabilizers. This is the only psychiatric disorder in which medications can prevent acute cycles of bipolar behavior. Once thought to help reduce manic behavior only, lithium and these anticonvulsants also protect against the effects of bipolar depressive cycles. If a client in the acute stage of mania or depression exhibits psychosis (disordered thinking as seen with delusions, hallucinations, and illusions), an antipsychotic agent is administered in addition to the bipolar medications. Some clients keep taking both bipolar medications and antipsychotics. Lithium. Lithium is a salt contained in the human body; it is similar to gold, copper, magnesium, manganese, and other trace elements. Once believed to be helpful for bipolar mania only, investigators quickly realized that lithium could also partially or completely mute the cycling toward bipolar depression. The response rate in acute mania to lithium therapy is 70% to 80%. In addition to treating the range of bipolar behaviors, lithium can also stabilize bipolar disorder by reducing the degree and frequency of cycling or eliminating manic episodes (Severus, Bauer, & Geddes, 2018). Lithium not only competes for salt receptor sites but also affects calcium, potassium, and magnesium ions as well as glucose metabolism. Its mechanism of action is unknown, but it is thought to work in the synapses to hasten destruction of catecholamines (dopamine, norepinephrine), inhibit neurotransmitter release, and decrease the sensitivity of postsynaptic receptors (Burchum & Rosenthal, 2018). Lithium’s action peaks in 30 minutes to 4 hours for regular forms and in 4 to 6 hours for the slow-release form. It crosses the blood–brain barrier and placenta and is distributed in sweat and breast milk. Lithium use during pregnancy is not recommended because it can lead to first-trimester developmental abnormalities. Onset of action is 5 to 14 days; with this lag period, antipsychotic or antidepressant agents are used carefully in combination with lithium to reduce symptoms in acutely manic or acutely depressed clients. The half-life of lithium is 20 to 27 hours (Burchum & Rosenthal, 2018). Anticonvulsant Drugs. Lithium is effective in about 75% of people with bipolar illness, both adults and children (Duffy & Grof, 2018). The rest do not respond or have difficulty taking lithium because of side effects, problems with the treatment regimen, drug interactions, or medical conditions such as renal disease that contraindicate use of lithium. Several anticonvulsants traditionally used to treat seizure disorders have proved helpful in stabilizing the moods of people with bipolar illness. These drugs are categorized as miscellaneous anticonvulsants. Their mechanism of action is largely unknown, but they may raise the brain’s threshold for dealing with stimulation; this prevents the person from being bombarded with external and internal stimuli. Carbamazepine (Tegretol), which had been used for grand mal and temporal lobe epilepsy as well as for trigeminal neuralgia, was the first anticonvulsant found to have mood-stabilizing properties, but the threat of agranulocytosis was of great concern. Clients taking carbamazepine need to have drug serum levels checked regularly to monitor for toxicity and to determine whether the drug has reached therapeutic levels, which are generally 4 to 12 µg/mL (Burchum & Rosenthal, 2018). Baseline and periodic laboratory testing must also be done to monitor for suppression of white blood cells. Valproic acid (Depakote), also known as divalproex sodium or sodium valproate, is an anticonvulsant used for simple absence and mixed seizures, migraine prophylaxis, and mania. The mechanism of action is unclear. Therapeutic levels are monitored periodically to remain at 50 to 125 µg/mL, as are baseline and ongoing liver function tests, including serum ammonia levels and platelet and bleeding times. Gabapentin (Neurontin), lamotrigine (Lamictal), and topiramate (Topamax) are other anticonvulsants sometimes used as mood stabilizers, but they are used less frequently than valproic acid. Value ranges for therapeutic levels are not established. Clonazepam (Klonopin) is an anticonvulsant and a benzodiazepine (a schedule IV controlled substance) used in simple absence and minor motor seizures, panic disorder, and bipolar disorder. Physiological dependence can develop with long-term use. This drug may be used in lithium or other mood stabilizers, but is not used alone to manage bipolar disorder. Aripiprazole (Abilify), brexpiprazole (Rexulti), and cariprazine (Vraylar) are dopamine system stabilizer antipsychotic medications used as adjuncts to other mood-stabilizing drugs. When other mood stabilizers alone are inadequate in controlling symptoms, the addition of these medications is effective in both the acute and maintenances phases of treatment (Mazza et al., 2018; Muneer, 2016). Second-generation antipsychotic medications are often used in conjunction with mood stabilizers or antidepressants to treat bipolar disorder. Ziprasidone (Geodon), lurasidone (Latuda), and quetiapine (Seroquel) are most effective. They prevent a “switch to mania” when persons are treated for a depressed episode and manage psychotic symptoms that are associated with mania in some people. Drug Therapy Research has shown that mood-stabilizing drugs such as lithium stimulate neuronal growth and reduce brain atrophy in people with long-standing mood disorders. Mood-Stabilizing Agents: Drugs Used to Treat Bipolar Disorder Lithium carbonate (Lithobid), the prototype, is a naturally occurring metallic salt that is used in patients with bipolar disorder, mainly to treat and prevent manic episodes. When used therapeutically, lithium is effective in controlling mania in 65% to 80% of patients. When used prophylactically, the drug decreases the frequency and intensity of manic cycles. Pharmacokinetics Lithium is well absorbed after oral administration, with peak serum levels in 1 to 3 hours after a dose and steady-state concentrations in 5 to 7 days. The drug is not metabolized; it is entirely excreted by the kidneys. Action The exact mechanism of action of lithium is unknown. However, the drug is known to affect the synthesis, release, and reuptake of several neurotransmitters in the brain, including acetylcholine, dopamine, GABA, and norepinephrine. It also stabilizes postsynaptic receptor sensitivity to neurotransmitters, probably by competing with calcium, magnesium, potassium, and sodium ions for binding sites. Lithium may also stimulate neuronal growth, exerting a neuroprotective effect on areas of the brain involved with mood. Use Lithium is the drug of choice for use in the treatment of manic episodes of bipolar disorder and as a maintenance treatment to decrease the number and intensity of manic episodes. Long-term therapy is the usual practice because of the high recurrence rate of bipolar disorder if the drug is discontinued. The prescriber may add an antiepileptic agent to the regimen. QSEN Alert: Safety Gradually tapering the dose over 2 to 4 weeks delays the recurrence of symptoms. It is important to note that doses should be relatively low initially and may increase gradually according to regular measurements of serum drug levels. Dosage is based on serum drug levels, control of symptoms, and occurrence of adverse effects. Measurements of serum levels are required for two reasons: (1) therapeutic doses are only slightly lower than toxic doses and (2) patients vary widely in rates of lithium absorption and excretion. Thus, a dose that is therapeutic in one patient may be toxic in another. Use in Patients With Renal Impairment Adequate renal function is a prerequisite for lithium therapy. The proximal renal tubules reabsorb approximately 80% of a lithium dose, and the amount of reabsorption depends on the concentration of sodium in the tubules. A sodium deficit causes more lithium to be reabsorbed and increases the risk of lithium toxicity. A sodium excess causes more lithium to be excreted (i.e., lithium diuresis) and may lower serum lithium levels to nontherapeutic ranges. QSEN Alert: Safety Therefore, if a patient with renal impairment or unstable renal function receives lithium, it is essential t levels be closely monitored. Use in Patients With Hepatic Impairment Caution is necessary when lithium is used in patients with hepatic impairment. Use in Patients With Critical Illness Lithium warrants caution in patients with critical illness. Lower doses are necessary in patients with conditions that impair lithium excretion (e.g., diuretic drug therapy, dehydration, low-salt diet, renal impairment, decreased cardiac output). It is necessary to discontinue lithium 1 to 2 days before surgery and resume it when full oral intake of food and fluids is allowed. QSEN Alert: Safety Lithium may prolong the effects of anesthetics and neuromuscular blocking drugs. Adverse Effects and Contraindications Common adverse effects of lithium include metallic taste, hand tremors, nausea, polyuria, polydipsia, diarrhea, muscular weakness, fatigue, edema, and weight gain. Contraindications include known sensitivity to the drug as well as pregnancy. (Lithium is a pregnancy category D medication.) Cardiac malformations are a common anomaly when lithium is administered in the first trimester. Preventing Interactions Drug Interactions: Lithium Drugs That Increase the Effects of Lithium • • • Alcohol and Increase the risk of dehydration, increasing the risk of lithium toxicity Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, indomethacin, Increase the serum level and the risk of toxicity Selective serotonin r Increase the risk of adverse effects such as confusion, drowsiness, and issues with coordination Drugs That Decrease the Effects of Lithium • Theophylline Increases renal excretion Administering the Medication Before beginning lithium therapy, it is important to obtain baseline studies of renal, cardiac, and thyroid status because adverse drug effects involve these organ systems. Baseline electrolyte studies are also necessary. When lithium therapy begins, it is necessary to measure the serum drug concentration two or three times weekly in the morning, 12 hours (trough) after the last dose of the drug. For most patients, the therapeutic range of serum drug levels is 0.5 to 1.2 mEq/L (SI units, 0.5 to 1.2 mmol/L). Serum lithium levels should not exceed 1.5 mEq/L because of the risk of serious drug toxicity. Doses of lithium should decrease after mania is controlled. During long-term maintenance therapy, it is necessary to measure serum lithium levels at least every 3 months. People should take lithium with food to decrease the risk of nausea and vomiting. Assessing for Therapeutic and Adverse Effects The nurse observes for decreases in manic behavior and stability in mood swings. Therapeutic effects do not occur until approximately 7 to 10 days after therapeutic serum drug levels are attained (1 to 1.5 mEq/L with acute mania; 0.6 to 1.2 mEq/L for maintenance therapy). In mania, a person usually takes a benzodiazepine or an antipsychotic drug to reduce agitation and control behavior until the lithium takes effect. The nurse also observes for the presence of a metallic taste, hand tremors, nausea, polyuria, polydipsia, diarrhea, muscular weakness, fatigue, edema, and weight gain. Patient Teaching Patient Teaching Guidelines for Lithium General Considerations • • • • • • Take lithium as directed to maximize therapeutic bene]its and minimize adverse effects. Do not alte lifelong. Keep scheduled of]ice or clinic visits for blood tests. Regular measurements of blood lithium levels Report for measurements of lithium blood levels as instructed and do not take the morning dose of Accurate measurement of serum drug levels requires that blood be drawn approximately 12 hours Do not take diuretic medications without consulting a health care provider. Diuretics cause loss of Maintain a normal diet, including consistent salt and adequate ]luid intake. Loss of salt in sweat inc activities that cause excessive perspiration, such as sweating during heavy exercise, sauna use, or o sweat increases the risk of adverse effects from lithium. Lithium can harm an unborn baby. If you are a woman of childbearing age, use an effective form of immediately if you become pregnant. If signs of overdose occur (e.g., vomiting, diarrhea, unsteady walking, tremor, drowsiness, muscle w or other health care provider immediately. Self or Caregiver Administration • • • Take with food or milk or soon after a meal to decrease stomach upset. Do not alter dietary salt intake. Decreased salt intake (e.g., low-salt diet) increases risk of adverse e therapeutic effects. Drink 8 to 12 glasses of ]luids daily; avoid excessive intake of caffeine-containing beverages. Excess lithium and reduce the effectiveness of the drug. Also, caffeine has a diuretic effect, and dehydratio Other Drugs in the Class Atypical antipsychotics are used to decrease dopamine activity in the treatment of the mania phase of bipolar disorder, including reducing acute mania, psychomotor agitation, and psychosis. Currently, aripiprazole, olanzapine (monotherapy or combination with fluoxetine), quetiapine, risperidone, and ziprasidone are approved by the FDA for this indication. Additionally, there is a potential risk for extrapyramidal signs and withdrawal symptoms in newborns whose mothers took these drugs during the third trimester of pregnancy. Aripiprazole (Abilify, Abilify Maintena, Abilify MyCite) is used to treat acute manic and mixed bipolar disorder adults and in children and adolescents aged 8 to 17 years. The drug is well absorbed with oral administration; is highly protein bound, metabolized in the liver; and is excreted in the urine and feces. Adverse effects include headache, somnolence, sedation, fatigue, dizziness, nausea, and vomiting. In May 2016, the FDA issued a Black Box Warning regarding aripiprazole; use placed the patient at risk for the development of compulsive or uncontrollable urges to gamble, shop, binge eat, or have sex. The nurse must educate the patient and family about this risk. Olanzapine (ZyPREXA, ZyPREXA Relprew, ZyPREXA Zydis) is prescribed as monotherapy for the treatment of acute, mixed, or manic episodes associated with bipolar disorder and in combination with fluoxetine (Symbyax) for the treatment of depressive episodes associated with bipolar disorder. The drug is predominately excreted in the urine and feces. Reported adverse effects, which are dose dependent, include somnolence, extrapyramidal symptoms, dizziness, weight gain, constipation, and xerostomia. In May 2016, the FDA issued a Black Box Warning concerning olanzapine because it can cause a drug reaction with eosinophilia and systemic symptoms. DRESS (drug reaction with eosinophilia and systemic symptoms) consists of a rash or exfoliative dermatitis. In addition, the patient may develop pancreatitis, nephritis, or pneumonitis. Quetiapine (Seroquel) is an atypical antipsychotic used for the treatment of bipolar disorder and schizophrenia. This drug is not recommended for dementia-related psychosis. It has antagonist effects on serotonin and dopamine. Excretion is in the urine and feces. Quetiapine may cause drowsiness, dizziness, decreased vision, fatigue, and weight gain. It should be administered without food or with 300 calories or less. Administration with food increases the peak serum concentration. Risperidone (Perseris, RisperDAL, RisperDAL Consta) is an atypical antipsychotic used alone or in combination with lithium or valproate for the treatment of acute mania or mixed episodes. The drug is approved by the FDA for use in adolescents aged 10 to 17 years with type I bipolar disorder. It is administered orally and intramuscularly and is well absorbed after oral administration. Risperidone is metabolized in the liver and predominately excreted in the urine. The drug enters breast milk. Adverse effects include significant weight gain, insomnia, sexual dysfunction, and photosensitivity. Neuroleptic malignant syndrome and tardive dyskinesia reportedly occur. Orthostatic hypotension may be present during the first few weeks of therapy. A Black Box Warning for risperidone reports that increasing mortality occurs in elderly patients with dementia-related psychosis. Ziprasidone (Geodon) is another atypical antipsychotic used for the treatment of bipolar disorder in adults. The exact mechanism of action is unknown. The drug is well absorbed, is highly protein bound, and is excreted in feces and urine. Adverse effects include dizziness, drowsiness, and lightheadedness. Other Medications Used to Treat Bipolar Disorder Anticonvulsants are also used as mood-stabilizing agents in bipolar disorder because they modify nerve cell function. Carbamazepine (Carbatrol, Epitol, TEGretol, TEGretol-SR), lamotrigine (LaMICtal, LaMICtal ODT, LaMICtal Starter, LaMICtal, and others), and valproate (Depakote, Depakote ER, Depakote Sprinkles) are currently approved by the FDA for treating bipolar disorder. The drugs are typically used for patients who do not respond to lithium. Other anticonvulsants (e.g., gabapentin, topiramate, oxcarbazepine) are being studied and used off-label for their effects in bipolar disorder, but they do not have FDA approval for this use. QSEN Alert: Safety Institute suicide precautions for at-risk patients. These usually involve close observation, often on a one environment. For patients hospitalized on medical–surgical units, transfer to a psychiatric unit may be ne