Meds For Bipolar 2

Therapy and medication

While bipolar disorder used to be treated primarily with psychotropic drugs, experts now agree that a combination of medication and psychotherapeutic or psychosocial treatment approaches is most promising. © DNY59 / istockphoto.com Nevertheless, treatment with psychotropic drugs remains the main focus, because without appropriate medication, stabilization of manic or depressive mood is unlikely to occur, and even in phases of stable mood, relapse is very likely. Psychotherapy can usefully supplement this treatment and provide sufferers with skills to help them cope better with their illness.

Therapy with psychotropic drugs

The type of medication varies depending on the phase of the illness. Acute manic phases are usually treated with neuroleptics (antipsychotics). The typical neuroleptic haloperidol or the atypical neuroleptics risperidone, quetiapine or olanzapine are mainly used. In a depressive phase, antidepressants, especially selective serotonin-norepinephrine reuptake inhibitors (SSNRI) or selective serotonin reuptake inhibitors (SSRI) are usually given. Unlike in unipolar depression, these are often combined with other medications, usually an atypical neuroleptic, for example olanzapine, quetiapine, or a mood stabilizer, for example lamotrigine. The aim here is to stabilize the mood in the long term and prevent it from tipping over into mania. (Drug treatment of depression). Mixed episodes are particularly difficult to treat because of the simultaneous manic and depressive symptoms. Usually, several medications are combined, including atypical neuroleptics, antidepressants, and mood stabilizers. A key element of therapy is the prevention of relapse. Mood stabilizers such as lithium or the antiepileptic drugs valproic acid, lamotrigine or carbamazepine are used for this purpose. Lithium has been shown to be the most effective medication for relapse. The problem with this medication, however, is that too high a level of lithium can quickly develop in the blood, leading to sometimes dangerous side effects such as tremors, nausea, vomiting, and cardiac arrhythmias. Among the antiepileptic drugs, lamotrigine effectively prevents mainly depressive phases, while valproic acid and carbamazepine mainly prevent manias in the long term. If manic phases are prominent in a patient, he or she is often also advised to take an atypical neuroleptic together with lithium or an antiepileptic drug in the long term to prevent relapses.

Psychotherapeutic approaches

Several psychotherapeutic and psychosocial therapies have been shown to be effective for bipolar disorder in various studies. These include family-oriented therapy, cognitive behavioral therapy, interpersonal and social rhythm therapy, and group psychoeducation. These approaches can help individuals recover more quickly from a depressive or manic episode, experience another episode of illness later, and experience significantly less impairment at work and in their social relationships. An important goal of therapy is relapse prophylaxis: this is intended to prevent further phases of the illness or to delay them as long as possible. The focus is on psychoeducation for the patient and his or her relatives, in which all those involved receive information about the development of the disease. Patients also learn how to cope better with stress, recognize early warning symptoms of a manic or depressive episode in good time, respond with appropriate strategies and lead a more balanced, stable life overall. In addition, we work with the patient to ensure that he or she takes his or her medication regularly. During a depressive episode, psychotherapy is very similar to treatment for unipolar depression (depression). Here, for example, the aim is first to create a regular daily routine and motivate the patient to be more active and engage in pleasant activities. In addition, negative thoughts are questioned and the patient is encouraged to resume social contacts. However, a key difference in bipolar disorder is that the therapist must always be alert to a possible tipping into a hypomanic or manic mood. During an acute manic or mixed phase or a severe depressive phase, psychotherapy is hardly possible. Here, the focus is on treatment with medication, which in most cases takes place as an inpatient in a clinic. In a hypomanic episode, treatment with appropriate medication is also important, but hospitalization is usually not necessary. In this case, it makes sense to continue psychotherapy because it can help stabilize the patient.

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Couple and family therapy

Couple and family therapy can be very helpful in bipolar disorder and can significantly reduce the likelihood of relapse. In particular, Miklowitz’s (1997, 2010) family therapy approach has a very positive impact on relapse rates. Important aspects in this approach are education about the disorder and its causes (psychoeducation), help in solving everyday problems (problem-solving training), improving communication skills, and assistance in preventing relapse. Couple and family therapy is particularly useful in the case of bipolar disorder because conflicts often arise in the family or partnership as a result of the illness. These can trigger strong mood swings in the patient and thus increase the probability of slipping into mania or depression. For example, it often happens that relatives already find the patient’s mood conspicuous and worry, while the patient himself does not perceive his condition as problematic. If the relatives try to exert influence, for example by making statements such as “You’re behaving very differently than usual, you’d better go to the doctor,” the affected person can quickly feel patronized. On the other hand, the relatives are also often heavily burdened by the disease. In therapy, all family members have the opportunity to address their views and problems – in general and in connection with the disease. Over time, they learn to better understand each other’s points of view, which can make it possible to find a solution that satisfies everyone.

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Cognitive behavioral therapy

This form of therapy has also proven helpful for bipolar disorder. Therapist and patient first work together to determine which factors contributed to the development of the disorder and which specific risk factors promote the occurrence of manic and depressive phases of the illness. Patients are usually asked to keep a mood diary, from which mood swings and their triggers can be identified in retrospect. The therapist works out with the patient how important it is to take the medication regularly and encourages him to adopt a more balanced rhythm of life. In addition, typical thoughts and thought patterns that can promote the onset of mania or depression are worked out, for example, thoughts such as “I can do everything”, “My special abilities are not properly appreciated”. In therapy, the individual warning signals that can be signs of incipient mania or hypomania or depression are also worked out, for example that someone wants to experience more than usual, drinks more alcohol or works significantly more than usual. Patients also practice distinguishing between everyday mood swings in response to certain situations, for example anger at criticism, joy at passing an exam, and emotional states that may be the first signs of mania or depression. A contingency plan is then agreed upon to help the individual respond to the early warning signs in a meaningful way. This plan usually contains several stages: for example, when the first mild symptoms appear, the patient should first find more rest by doing relaxation exercises in the evening and not going to bed too late. If the symptoms continue to increase, the next step may be to take medication as needed and make an additional appointment with the therapist. If the symptoms are severe, it is agreed that the patient will contact an emergency clinic. In cognitive behavioral therapy, patients also learn to improve general psychological skills, for example, to better express their own feelings and needs, to better manage conflicts and to deal more openly with their illness. Often, key attachment figures are also included in therapy so that conflicts can be resolved together.

Therapist List Behavioral Therapy

Interpersonal and Social Rhythm Therapy

This approach assumes that manic and depressive mood swings are triggered primarily by an irregular sleep-wake rhythm. The focus of therapy is therefore on helping patients maintain a regular sleep-wake rhythm and a relatively regular daily routine. At the same time, they are helped to solve individual and interpersonal problems.

Other approaches

Psychoeducational and sociotherapeutic approaches have also proven helpful in bipolar disorder. Here, patients receive information about the development of their disorder and how to better manage their symptoms. Furthermore, self-help groups can also be helpful: they allow patients to share difficulties with others and receive helpful information on how to deal with their own illness.

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Choosing a drug can be difficult because all drugs have significant adverse effects, drug interactions are common, and no drug is universally effective. Selection should be based on what has been previously effective and well tolerated in a particular patient. Without prior experience (or when it is unknown), the choice is based on the patient’s history (looking at the adverse effects of the specific mood stabilizer) and the severity of symptoms. For less severe acute episodes in patients without contraindications (e.g., renal disease), lithium is a good first choice for both mania and depressive episodes. Because the onset of action is slow (4-10 days), patients with significant symptoms may also receive an anticonvulsant or a 2nd generation antipsychotic. For patients with depression the anticonvulsant lamotrigine may be a good choice. For bipolar depression, the best evidence suggests treatment with quetiapine or lurasidone alone or the combination of fluoxetine and olanzapine. When remission is achieved, preventive treatment with mood stabilizers is indicated for all patients with bipolar I disorder (bipolar I is defined by the presence of at least one full-blown manic episode and mostly depressive episodes). If episodes recur during maintenance therapy, clinicians should determine whether adherence is low and, if so, whether the lack of adherence occurred before or after the relapse. The reasons for poor adherence should be elicited to determine whether more acceptability of treatment could be achieved by switching to a different mood stabilizer or changing the dose. As many as two-thirds of patients with uncomplicated bipolar disorder respond to lithium, which attenuates bipolar mood swings but has no effect on normal mood. Regardless of whether lithium or mood stabilizers are used, breakthroughs are more likely in patients with mixed state Mixed forms Bipolar disorder is characterized by manic and depressive episodes that may alternate, although in many patients one or the other is dominant. The exact cause… Learn more , rapid-cycling forms of bipolar disorder (usually defined as ≥ 4 episodes/year), comorbid anxiety disorder Overview of Anxiety Disorders Everyone experiences fear and anxiety from time to time. Fear is an emotional, physical, and behavioral response to a specific external threat (e.g., an intruder… Learn More , Substance Abuse Substance Use Disorders Substance use disorders are a type of substance-related disorder that involve a pathological pattern of behavior in which patients continue to use a substance even though… Learn more or a neurological disorder. Lithium carbonate is started at 300 mg p.o. 2 or 3 times/day and titrated up to a range of 0.8-1.2 mEq/l based on steady-state blood levels and tolerance. Levels should be determined after 5 days at a stable dose and 12 h after the last dose. Target drug levels in maintenance therapy are lower and are approximately 0.6-0.7 mmol/l. Higher levels in maintenance therapy are more protective against manic (but not depressive) episodes, but they have more adverse effects. Adolescents with very good renal function require higher doses, and older patients require lower doses. Lithium can cause sedation and cognitive impairment directly or indirectly (by causing hypothyroidism) and often exacerbates acne and psoriasis. The most common acute mild side effects are: fine-beat tremor, fasciculations, nausea, diarrhea, polyuria, polydipsia, and weight gain (which is partly attributable to consumption of high-calorie beverages). These effects are generally transient in nature and often respond to a slight dose reduction, splitting the dose (e.g., 3 times/day), or the use of sustained-release preparations. Once the dosage is established, the entire dose should be taken after the evening meal. This dosage may improve adherence. A beta-receptor blocker (e.g., atenolol 25-50 mg p.o. once daily) may control violent tremor; however, some beta-receptor blockers (e.g., propranolol) may worsen depression. Early signs of acute lithium intoxication are gross tremor, increased deep tendon reflexes, persistent headache, vomiting, and confusion; they may progress to stupor, seizures, and arrhythmias. Toxicity is more likely to occur in the following:

Elderly patients
Patients with decreased creatinine clearance.
Those with sodium loss (for example, due to fever, vomiting, diarrhea, or use of diuretics)

Thiazide diuretics, ACE inhibitors, and nonsteroidal anti-inflammatory drugs other than aspirin may contribute to hyperlithemia. Lithium blood levels should be determined every 6 months and with dose changes. Undesirable long-term effects of lithium include

Renal damage to the distal tubule occurring after ≥ 15 years of lithium treatment.

1. Presne C, Fakhouri F, Noël LH, et al: Lithium-induced nephropathy: rate of progression and prognostic factors. Kidney Int 64 (2):585-592, 2003.
2 Pawar AS, Kattah AG: Lithium-induced nephropathy. N Engl J Med 378 (11):1042, 2018. doi: 10.1056/NEJMicm1709438.

Anticonvulsants that act as mood stabilizers, particularly valproate and carbamazepine, are commonly used in acute mania and mixed states (mania and depression). Lamotrigine is effective for mood disorders and depression. The exact mechanism of action of anticonvulsants in bipolar disorder is not known, but GABAergic mechanisms (gamma-aminobutyric acid) and the G-protein signaling system may be involved. Their main advantages over lithium are greater therapeutic breadth and lack of renal toxicity. Valproate is given at a loading dose of 20-30 mg/kg, followed by 250-500 mg p.o. 3 times/day (extended-release formulations can be used); target blood levels range from 50 to 125 μg/ml. This approach does not result in more adverse effects than stepwise titration administration. Adverse effects include nausea, headache, sedation, dizziness, and weight gain; rare serious adverse effects include hepatotoxicity and pancreatitis. Carbamazepine should not be started with a loading dose but with 200 mg p.o. 2 times/day, gradually increasing in increments of 200-mg/day to target levels between 4 and 12 μg/ml (maximum 800 mg 2 times/day). Adverse effects include nausea, dizziness, sedation, and unsteadiness. Very serious adverse effects include aplastic anemia and agranulocytosis. Lamotrigine is administered at 25 mg p.o. once daily for 2 weeks, followed by 50 mg once daily for 2 weeks and then 100 mg/day for 1 week, and then may be increased by 50 mg per week as needed up to 200 mg once daily. Dosage is lower for patients taking valproate and higher for patients taking carbamazepine. Lamotrigine may cause a rash and rarely life-threatening Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) Stevens-Johnson syndrome and toxic epidermal necrolysis are severe hypersensitivity reactions of the skin. Most often, drugs, especially sulfonamides, antiepileptic drugs, and antibiotics are… Learn more cause, especially if the dosage is increased more quickly than recommended. While taking lamotrigine, patients should be asked to report any new rash, hives, fever, swollen glands, sores in the mouth and eyes, and swelling of lips or tongue.

Risperidone (usually 2 to 3 mg p.o. twice daily).
Olanzapine (usually 5 to 10 mg p.o. twice daily).
Quetiapine: (200-400 mg p.o. 2 times daily)
Ziprasidone (40 to 80 mg p.o. twice daily)
Aripiprazole (10 to 30 mg p.o. 1 time daily).

In addition, evidence suggests that these drugs may enhance the effects of mood stabilizers after the acute phase. In extremely hyperactive psychotic patients with low food and fluid intake, an i.m. antipsychotic plus supportive care may be appropriate in addition to therapy with lithium or an anticonvulsant. Lithium use during pregnancy is associated with an increased risk of cardiovascular malformations (especially Ebstein anomaly). However, the absolute risk for this particular malformation is quite low. Lithium use during pregnancy appears to increase the relative risk of congenital anomalies approximately 2-fold; this risk is similar to the 2- to 3-fold increased risk of congenital malformations associated with carbamazepine or lamotrigine use and much lower than the risk associated with valproate use. Extensive studies of the use of 1st-generation antipsychotics and tricyclic antidepressants during early pregnancy found no cause for concern. The same is true for SSRIs, with the exception of paroxetine. Data on the risks of 2nd-generation antipsychotics to the fetus are sparse to date, although these drugs are more widely used in all phases of bipolar disorder. Medication use (especially lithium and SSRIs) before birth may have carry-over effects on the newborn. Treatment decisions are complicated by the fact that teratogenic effects may have already occurred in an unplanned pregnancy by the time physicians become aware of the problem. Consultation with a perinatal psychiatrist should be considered. In any case, discussion of the risks and benefits of treatment with patients is important.

1. Tomson T, Battino D, Perucca E: Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol 15 (2): 210-218, 2016. doi: 10.1016/S1474-4422(15)00314-2.

Meds For Bipolar 2.