Individualizing Treatment Options in BDI - Psychiatric Times

Adherence, comorbidities, and attraction efficacy successful bipolar I disorder (BDI) were the themes discussed by Vladimir Maletic, MD, MS, and Andrew J. Cutler, MD, successful a caller PsychView customized video series.

Both Maletic, a objective prof of psychiatry and behavioral sciences astatine University of South Carolina School of Medicine successful Greenville, and Cutler, main aesculapian serviceman astatine Neuroscience Education Institute successful Carlsbad, California, and an subordinate objective prof of psychiatry astatine SUNY Upstate Medical University successful Syracuse, said overmuch has has changed since they were successful aesculapian school.

“When we trained, we were taught determination was a portion of the encephalon that was liable for slump and determination was thing incorrect with this portion of the brain,” said Cutler. “But we present cognize it’s overmuch much complicated.”

“As we elucidate immoderate of the pathophysiology underlying bipolar disorder, we are realizing that symptoms of bipolar unwellness representation much easy connected dysfunction of a functional encephalon network, and their communication, than they bash to transmitter systems,” Maletic added.

“In addition, determination are issues with accrued motoric enactment successful mania,” Maletic continued. “These individuals are restless and agitated and often pacing. On the different hand, salience web besides seems to person heightened enactment and, therefore, determination is perchance a narration with grandiosity….The alleged default mode network, which successful portion has to bash with self-reflection of monitoring, seems to person decreased enactment successful mania.”

Adding to the Challenge

Psychiatric comorbidities tin complicate the diagnostic process and the attraction selection. The 2 astir communal comorbidities with BD are substance usage disorders and anxiety, Cutler said.

Attention-deficit/hyperactivity upset (ADHD) is the 3rd astir communal comorbidity successful patients with BD, helium added. “Even if patients don’t conscionable afloat criteria for ADHD, astir of them person immoderate aspects of it, particularly problems with sustained attraction and moving memory.

The 4th astir communal comorbidity is binge-eating disorder, Cutler said. “I bash deliberation that there’s an constituent of dopamine dysregulation that goes on. And, if you deliberation astir it, ADHD, substance usage disorder, binge-eating disorders, these are disruptions of the dopamine system, particularly information reward. And that whitethorn beryllium wherefore immoderate of our effectual medications look to stabilize the dopamine system.”

In individualizing attraction strategies, it is important and harmless to code psychiatric comorbidities successful summation to BDI, Cutler and Maletic said.

For comorbid ADHD and BD, for example, utilizing stimulants tin beryllium considered, Cutler said, citing 2 ample meta-analyses supported their use.

“What the researchers recovered was that arsenic agelong arsenic the diligent is adequately temper stabilized—either with a accepted temper stabilizer oregon atypical antipsychotic—not lone does adding the stimulant not wounded the patient, it really improves their mood, their attention, and assorted different issues,” helium explained. “Of course, they person to beryllium adequately temper stabilized, and I person to beryllium comfy that they are not going to beryllium actively abusing the medication.”

Similarly, comorbid anxiousness upset mightiness power Cutler’s attraction decisions. “I thin to usage atypical antipsychotics present arsenic a foundation, and past I’ll adhd either lithium oregon lamotrigine, possibly divalproex,” Cutler said. “Some of the atypical antipsychotics look to beryllium amended than others for treating comorbid anxiety.”

Cutler added that helium besides considers selective serotonin reuptake inhibitors (SSRIs). “One spot wherever I deliberation determination whitethorn beryllium a relation for SSRIs is idiosyncratic who has a existent obsessional anxiousness picture,” helium said. “A small serotonin whitethorn assistance with obsessionality. But, successful general, I bash effort to debar what I telephone traditional antidepressants oregon non–mood stabilizing antidepressants.

“The bipolar encephalon is conscionable not good buffered,” Cutler said. “So if you flood it with monoamines, it’s going to spell disconnected the road...You’ll spell disconnected into a temper episode.”

Addressing Bipolar Depression

Maletic and Cutler some agreed that it is important to commencement with an FDA-approved medicine erstwhile processing a attraction strategy for bipolar depression due to the fact that that presumption indicates that the cause is some efficacious and safe. However, they noted that determination is disorder astir what is and is not FDA approved.

“What’s absorbing is erstwhile you canvass audiences, they get [the reply to] this question incorrect each the time: What are the approved medications for bipolar depression? Well, it turns retired determination are 5 of them, and each 5 of them are atypical antipsychotics,” Cutler said. “Lithium, divalproex, carbamazepine, and lamotrigine are not approved for acute bipolar depression.”

Although not each antipsychotics are approved for mania, Cutler believes each would enactment for mania.

In presumption of choosing medications, Cutler said his “whole reasoning has changed.” He noted, “I inactive similar lithium, and I similar lamotrigine. Divalproex hasn’t worked arsenic good for slump for me, truthful I reserve that for idiosyncratic with a existent troublesome mania oregon predominant manias. It’s a bully antimanic. But I thin to usage the atypical antipsychotics.”

Cutler said the bulk of patients person recurrent depressions, with depressions lasting longer, and an accrued impairment associated much with a depressive authorities than with the manic state. Thus, helium looks for an cause that tin code and perchance forestall the depressions. He finds lamotrigine to beryllium a bully choice. He besides likes lithium for maintenance. However, if determination is an constituent of anxiety, helium considers quetiapine a “go-to medication” if the dose tin beryllium adjusted to minimize value and metabolic issues.

Although the American Psychiatric Association BD attraction guidelines antecedently advised the usage of antipsychotics acutely only, “the reasoning has perfectly changed,” Cutler said. “We person respective [antipsychotics] that are FDA approved for attraction attraction of bipolar disorder. Very often what I find is if a medicine works acutely for a patient, it usually continues to enactment if they proceed to instrumentality it. So I’m much apt to enactment with the medicine that helps them successful the acute phase.”

Cutler cautioned that the FDA requires monotherapy trials but admitted that the bulk of patients are connected much than 1 medication. “Bipolar upset is hard to dainty with conscionable 1 medication,” helium said. “We person 2 medications present that are FDA approved for bipolar slump successful operation with either lithium oregon divalproex.”

It is besides important to see associated oregon breakthrough symptoms, Cutler added. “You mightiness beryllium dealing with insomnia oregon anxiousness or... ADHD.”

Maletic and Cutler noted that clinicians look to beryllium drawn to antidepressants arsenic a tool, adjacent though determination are issues with doing so.

“I deliberation our brains conscionable privation to spell to an antidepressant,” Cutler said. “This is simply a occupation with nomenclature.... It’s precise unfortunate that we person a people of drugs called antidepressants and a people of drugs called antipsychotics. It’s conscionable not the mode they work.

“I similar to separate betwixt what I telephone the traditional non–mood stabilizing antidepressants, which are predominantly reuptake inhibitors, and what I telephone the mood stabilizing antidepressants, which are, successful fact, immoderate of the atypical antipsychotics,” Cutler said.

“Another absorbing information is that each of the antipsychotics, whether archetypal procreation oregon 2nd generation, enactment beauteous good for psychosis and astir apt for mania, but they don’t each person arsenic beardown an antidepressant signal,” helium added. “That’s what I find fascinating due to the fact that respective of the newer atypical antipsychotics person been studied either arsenic adjunct for unipolar large slump oregon for bipolar depression, and determination person been immoderate failures. Then determination are immoderate that person had precise robust antidepressant signals successful that setting.”

A New Look astatine LAIs

What astir the long-acting injectable (LAI) antipsychotics? Cutler and Maletic are impressed with however good they enactment and however good they person been accepted by patients.

“I’ll ne'er hide erstwhile I was archetypal contacted to beryllium an researcher connected a survey of long-acting risperidone, [there was] microsphere mentation with each 2-week injection for bipolar upset for maintenance. I conscionable thought that was benignant of retired there,” Cutler said. “I conjecture I’d ever associated the LAIs with schizophrenia and psychotic disorders.

“I thought I was going to person occupation recruiting for this study,” helium shared. “I thought patients with bipolar upset thin to beryllium higher functioning. Are they going to privation to person a shot? I was amazed however galore radical with bipolar disorder, erstwhile fixed this option, accepted the option.”

Those studies yet led to the FDA support of risperidone long-acting microsphere preparation. “We besides present person an aripiprazole long-acting injectable, aripiprazole monohydrate,” Cutler said.

“That acquisition truly changed my thinking,” helium explained. “Sometimes I emotion erstwhile I’m proven wrong. I benignant of emotion erstwhile I’m benignant of flat-footed similar that and conscionable don’t see the options.”

Another payment of LAIs is their interaction connected adherence. According to Maletic, studies amusement that betwixt 40% to 60% of individuals with BD bash not adhere to treatment.

“If we inquire our audience, ‘What is 1 of the biggest challenges you look successful managing bipolar disorder?’...near the apical is going to beryllium adherence,” Cutler explained.

“[BD] works connected parts of the encephalon that person to bash with penetration and judgment,” helium added. “I deliberation radical with bipolar upset often are not precise self-aware.... They don’t ever person the champion penetration and judgment.... So they whitethorn think, ‘Well, it’s not that bad. I don’t request to instrumentality medication.’”

Thus, Cutler shares the LAIA enactment with patients due to the fact that they whitethorn similar it for each the aforesaid reasons patients with schizophrenia similar it: Patients bash not person to spell spot the doc arsenic often, they bash not person to retrieve to instrumentality oregon deliberation astir a medication, and it is discreet—nobody volition “catch” them taking a pill.

Plus, Cutler said helium believes tolerability is amended with LAIs compared with oral medications. “If you deliberation astir the pharmacokinetics of an oral drug, the medicine has a batch of peak-to-trough variability, whereas the LAIs thin to person a overmuch smoother humor level with little peak-to-trough variability,” helium explained.

That, successful turn, impacts the adverse effects. “We each cognize that astatine highest levels, you tin person much broadside effects,” Cutler said. “There is immoderate grounds that determination whitethorn adjacent beryllium little hazard of question disorders with [LAIs].

Based connected the schizophrenia literature, LAIs besides whitethorn beryllium amended astatine preventing deterioration and preserving the brain, Cutler said. “I thin to deliberation of bipolar present a small much than I utilized to arsenic a perchance neurodegenerative oregon neuroprogressive disorder,” helium explained. “I had a prof years agone who said to me, ‘Never fto anybody enactment manic oregon psychotic due to the fact that it is atrocious for the brain.’ There is present grounds that that whitethorn beryllium true. As we cognize with consequent manic oregon consequent depressive episodes, you tin spot a alteration not lone successful encephalon insubstantial but besides successful cognitive performance. Use of a long-acting injectable whitethorn not lone forestall objective relapse—it whitethorn beryllium illness modifying.”

Although Cutler said it is not realistic to spot LAIs arsenic first-line treatment, the enactment whitethorn emergence to the apical of the database for patients who “are susceptible to relapse with oral medications, either owed to the unwellness itself oregon to their trouble with adherence.”

Still, helium likes the thought of starting the LAI speech and detailing retired however it mightiness beryllium beneficial erstwhile the diligent is struggling oregon finds themselves successful hard situations, similar successful jailhouse oregon successful the hospital. Peter Weiden, MD, a schizophrenia adept and colleague, enactment it succinctly to him, Cutler said. “Andy, you connection them LAI, the archetypal clip they’ll say, ‘No.’ You connection the 2nd time, they say, ‘No.’ You connection the 3rd time, they accidental ‘No.’ The 4th time, they’ll say, ‘Why didn’t you archer maine astir this before?’”

It is each successful the presentation, Cutler noted. “You don’t say, ‘Would you similar an injection? Do you privation a changeable of your medicine?’ You would say, ‘Are you funny successful a modality that has been shown to forestall relapse and the consequences of relapse and that you lone person to take, for instance, erstwhile a period oregon lone person to deliberation astir erstwhile a month? By the way, the mode it’s delivered is by an injection—a long-acting injection.’ I recovered I get amended occurrence that way.”

Concluding Thoughts

Maletic and Cutler emphasized that it is important to surface each depressed diligent for BD and to marque the close diagnosis arsenic aboriginal arsenic possible. “The sooner you tin admit and diagnose bipolar, the sooner you tin institute effectual evidence-based treatments,” Cutler said.

The adjacent measurement is to beryllium thoughtful astir the attraction choices. “As we person much options, it’s truly important to deliberation astir individualizing attraction not lone for the temper authorities oregon the temper occurrence you mightiness beryllium treating oregon the benignant of signifier that the diligent has with respect to manias versus depressions, but besides assorted comorbidities and diligent preferences. It’s precise important to offer—and get comfy with—all of the antithetic options,” Cutler said.

“I similar to accidental that if I lone had a 5 robust successful my play bag, I don’t deliberation I’d beryllium arsenic bully a golfer arsenic I americium with my afloat acceptable of clubs. The much antithetic tools—the much clubs you person successful your bag, truthful to speak—the amended outcomes we’re going to person for our patients.”

To ticker this Around the Practice program, sojourn https://www.psychiatrictimes.com/psych-view/expert-perspectives-on-the-clinical-management-of-bipolar-1-disorder.