Optimizing bipolar I disorder management with a monthly atypical long-acting injectable antipsychotic
History and presentation
This is a case of a 32-year-old overweight gentleman with a long-standing history of bipolar I (BP-I) disorder since the age of 17 years. The illness was precipitated by the death of both parents in a road traffic accident in 2004. Over the years, the patient had recurring hypomanic episodes, and had symptoms of hallucinations, persecutory delusion and depressive episodes, requiring frequent hospitalizations. His social situation was made more difficult as he was the only son and had he inherited a substantial fortune from his parents. He had a chaotic lifestyle with illness complicated by concomitant alcohol and marijuana abuse. He was being manipulated by his friends for money, had married and divorced once with a daughter in the custody of his ex-wife, and had been involved in medicolegal cases due to drink-driving.
Treatment and response
Despite treatment with various antipsychotic medications, including haloperidol (10–20 mg), lithium (1,000 mg), valporate (900 mg), olanzapine (5–10 mg), quetiapine (200–400 mg), aripiprazole (10–20 mg orally) and haloperidol decanoate (100 mg intramuscularly once every 4 weeks), the patient did not respond well and continued to have multiple hypomanic and depressive episodes over the years. He had poor compliance to oral antipsychotic medications and complained of treatment side effects, including drowsiness and the extrapyramidal symptom of akathisia, which worsened with concomitant alcohol and drug abuse. The treatment option of atypical long-acting injectable (aLAI) aripiprazole once-monthly (AOM) 400 mg as maintenance therapy was eventually put forward and readily accepted by the patient and his caregiver.
The patient was started on atypical LAI AOM 400 mg in June 2018 and responded well to treatment, with no significant weight gain. Significant improvements in his symptoms were observed in August 2018. He is being maintained on atypical LAI AOM 400 mg and has remained relapse-free in terms of hypomanic and depressive episodes since September 2018. His thoughts, response, expression and attitude normalized, and negative symptoms improved within a few months of starting atypical LAI AOM 400 mg. He was not binge-eating, was no longer abusing alcohol or cocaine, and was able to function well and return to work.
Our patient suffered from a long-standing BP-I disorder, was overweight, had issues with alcohol and drug abuse, and lacked consistent adherence to oral antipsychotic medications due to their side effects as well as his disordered mental state, which led to functional impairment and inadequate control of his illness. Treatment with atypical LAI AOM 400 mg achieved significant amelioration of his symptoms, and was well tolerated without side effects. The patient has remained relapse-free on atypical LAI AOM since September 2018.
According to the 2016 treatment guideline of the British Association for Psychopharmacology, long-term treatment is the preferred strategy following a single episode of severe mania in patients with BP-I disorder. Atypical LAI aripiprazole is recommended if prophylaxis against recurrent mania is required.1
Aripiprazole is a dopamine receptor partial agonist whose effects are mediated through a combination of partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at 5-HT2A receptors.2 Aripiprazole in a LAI formulation has a half-life of 29.9–46.5 days depending on the dose, with steady-state plasma concentrations attained by the fourth monthly injection, thus allowing gradual absorption following intramuscular injection and a delay in onset of potential adverse events.3
In a double-blind, placebo-controlled, 52-week randomized withdrawal study, 266 patients with a diagnosis of BP-I disorder experiencing a manic episode were randomized to receive AOM 400 mg or placebo following sequential stabilization on oral aripiprazole and AOM 400 mg. Compared with placebo, AOM 400 mg significantly delayed the time to recurrence of any mood episodes (hazard ratio, 0.45; 95 percent confidence interval [Cl], 0.30 to 0.68; p<0.0001) and reduced the rate of recurrence of any mood episodes (26.5 percent vs 51.1 percent; p<0.0001), with the main difference observed in the recurrence rate of manic episodes (p<0.001).4 (Figure)
Treatment with atypical LAI AOM 400 mg also resulted in a significant improvement in young mania rating scale (YMRS) total score from baseline to week 52 (adjusted mean, -3.09; 95 percent CI, -5.01 to -1.17, p=0.002) compared with placebo, with consistently significant between-group differences observed from week 14. The time to treatment discontinuation due to all causes was significantly longer with AOM vs placebo (median, 345 days vs 170 days; p=0.0026).4
A follow-on, open-label, multicentre study involving patients with BP-I disorder who were naïve to (de novo group) or experienced with AOM 400 mg (rollover group) from the above 52-week trial showed an overall discontinuation rate of 10.3 percent as a result of treatment-emergent adverse events (TEAEs) with AOM 400 mg, with akathisia (15.8 percent for de novo group vs 9.4 percent for rollover group), weight gain (14.8 percent vs 7.1 percent) and nasopharyngitis (12.7 percent vs 9.4 percent) being the most common TEAEs. Mean weight gain from baseline to last visit in the AOM 400 mg maintenance phase was 0.5 kg for the de novo group vs 0.6 kg for the rollover group.5 A previous review also showed a lower incidence of metabolic adverse events and weight gain with aripiprazole compared with risperidone, quetiapine and olazanpine.6
In the follow-on study, a majority (89 percent) of patients remained stable (defined as outpatient, YMRS total score ≤12, Montgomery-Asberg Depression Rating Scale [MADRS] total score ≤12, and no active suicidality; active suicidality defined as MADRS item 10 score ≥4, or “yes” on question 4/5 of the Columbia Suicide Severity Rating Scale) throughout the maintenance phase of AOM 400 mg treatment. The need for rescue medication, such as lithium or valproate, was minimal (<10 percent of patients). More than 70 percent of patients expressed a high level of satisfaction with AOM 400 mg treatment, and >65 percent rated a great improvement in side effects with AOM 400 mg relative to their previous medications.5
Timing is important in the management of BP-I disorder, as early start of atypical LAI AOM can help minimize biochemical abnormalities in the brain, reduce relapses, and ensure full recovery of mental state and function. Switching treatment from oral antipsychotics to atypical LAI AOM may also be considered in patients with rapid cycling episodes or frequent relapses who are noncompliant with oral medications.
It is also important to establish good rapport with the patients, maintain a stable doctor-patient relationship, and educate patients and their caregivers on drug compliance and symptom awareness to facilitate effective management of BP-I disorder and address patients’ fear of needles.
This case report illustrates the successful use of atypical LAI AOM as maintenance monotherapy for a patient with BP-I disorder in stabilizing biochemical abnormalities in the brain, leading to regain of mental and functional stability and return of normal self. Atypical LAI AOM was well tolerated in our patient without complaints of side effects.