California cocktail antidepressant

How do you choose a mood stabilizer?

Although many monotherapies are proven effective for one or more phases of bipolar disorder, few patients with a bipolar spectrum disorder can be maintained on monotherapy. Unfortunately for the practicing psychopharmacologist, almost all of the evidence for efficacy of mood stabilizers is based upon studies of monotherapies, whereas almost all patients with bipolar disorder are on combinations of therapeutic agents. In spite of having numerous evidence-based monotherapies, and learning all the lessons from empiric practice-based combinations of these treatments, bipolar disorder remains a highly recurrent, predominantly depressive illness with frequent comorbidities and residual symptoms. So, how does one get the best outcome for a bipolar patient? The answer proposed here is to learn the mechanisms of action of the known and putative mood stabilizers and their ancillary and adjunctive treatments, familiarize oneself with the evidence for their efficacy and safety in monotherapy trials, and then construct a unique portfolio of treatments one patient at a time. Evidence-based treatments for real-world management of bipolar disorder with combinations of mood stabilizers are relatively poorly researched. Many studies show that various atypical antipsychotics added to either lithium or valproate enhance antimanic efficacy. However, there are few studies of other combinations.

First-line treatments in bipolar disorder

Not all bipolar patients are complicated, especially at the onset of the illness, and when presenting in primary care in the depressed phase. So, before looking for complicated solutions, the best treatment choice for uncomplicated bipolar patients would first be to do no harm and thus to prescribe anything that avoids antidepressant monotherapy no matter what the current symptoms are. This begins with prudent determination of when depressive symptoms are due to bipolar versus unipolar depression, and if bipolar, may result in use of lamotrigine or an atypical antipsychotic or their combination while avoiding antidepressants.

Also, it should be appreciated that "mild mania" is not an oxymoron, and some bipolar patients present in this state, which suggests that treatment with either valproate, lithium, or an atypical antipsychotic monotherapy or their combination may reduce manic symptoms substantially. In primary care, there may be a wish to avoid valproate and lithium and even lamotrigine due to lack of familiarity with these agents, and to start with an atypical antipsychotic (while avoiding an antidepressant), with referral to a specialist if treatment results are not satisfactory.

That is the easy part. What about the majority of patients who present to psychopharmacologists with severe, recurrent, or mixed mania, rapid cycling symptoms, abundant comorbidity, and inadequate treatment responses with multiple residual symptoms after receiving all the treatments described above?

Combinations of mood stabilizers are the standard for treating bipolar disorder

Given the disappointing number of patients who attain remission from any phase of bipolar disorder after any given monotherapy or sequence of monotherapies, who can maintain that remission over the long run, and who can tolerate the treatment, it is not surprising that the majority of bipolar patients require treatment with several medications. Rather than have a simple regimen of one mood stabilizer at high doses and a patient with side effects but who is not in remission, it now seems highly preferable to have a patient in remission without symptoms no matter how many agents this takes. Furthermore, sometimes the doses of each agent can be lowered to tolerable levels while the synergy among their therapeutic mechanisms provides more robust efficacy than single agents even in high doses.

Several specific suggestions of combinations, or "combos," have enjoyed widespread use, even though for many of them there is little actual evidence-based data from clinical trials that their combination results in superior efficacy ( ). Because of the strong role of "eminence-basedFigure 8-12 medicine" (with sometimes conflicting recommendations by different experts), rather than evidence-based medicine, for combination treatments, some of the options are discussed here with a bit of whimsy. Nevertheless, treatment of bipolar disorders with rational and empirically useful combinations is a serious business, and the reader may find that several of these suggestions are useful for practicing clinicians to use in the treatment of some patients.

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The best evidence-based combinations consist of the addition of lithium or valproate to an atypical antipsychotic ( ). Although lithium, lamotrigine, and valproate have all been available for aFigure 8-12 long time, there are remarkably few controlled studies of their use together. Nevertheless, they all have different mechanisms of action and different clinical profiles in the various phases of bipolar illness; they can therefore be usefully combined in clinical practice due to practice-based evidence as