Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

74 O. Elhaj and J. R. Calabresestabilizer for patients diagnosed with BP-II disorder. Despite this study’s previouslymentioned limitations, it remains the first controlled study of its kind,especially with regard to the process of data analysis utilized, which is moregenerally suitable to prophylaxis studies.Concurrently, Frye et al.(2000) reported a placebo-controlled study of lamotrigineand gabapentin monotherapy in refractory mood disorders. The demographic profileof the study participants who were available for evaluation in all three treatmentphases (n ¼ 31) included 18 women and 13 men; 11 BP-I and 14 BP-II; 23 rapidcyclingand two non-rapid-cycling; and six unipolar patients.The design initially employed a double-blind random assignment to parallelarms. This was followed by 6-week cross-over trials, in which patients eventuallyreceived all three medications as monotherapy (gabapentin, lamotrigine, orplacebo). Between phases, a cross-over period of approximately 1 week was used.Patients were treated only with the study medications except for the following:four patients who continued receiving stable levothyroxine supplementation forcorrected primary hypothyroidism; one patient who continued receiving diuretictherapy for essential hypertension; and two patients, who each continued receivingstable prior medications (i.e., triiodothyronine and clonazepam). The number ofpatients randomized to lamotrigine (L), gabapentin (G), and placebo (P) were asfollows: PLG: 6; PGL: 5; LPG: 6; LGP: 6; GPL: 4; and GLP: 5. Lamotrigine wasinitially administered at a dose of 25 mg daily for the first week, and titrated up to300–500 mg/day for the fifth through sixth weeks. Gabapentin was administeredinitially at a dose of 900 mg/day and was titrated to 4800 mg by the fifth throughsixth weeks. After the three phases of the study were completed, the patients whohad responded to a particular phase (I, II, or III) were offered the option ofreturning to that phase, still on a blinded basis, for response confirmation.The primary outcome measure of overall improvement was the CGI scale thatwas modified for bipolar illness (CGI-BP). Supplementary ratings used in theevaluation and completion of the CGI response rating included prospective selfandobserver-rated life charting, Hamilton-D, Young Mania Rating Scale (YMRS),the Spielberger State Anxiety Scale, and Brief Psychiatric Rating Scale (BPRS).CGI-BP change determinations were made by a consensus of blinded researchphysicians and clinicians, both in comparison with the previous phase of illnessand the worst phase of documented illness. Previous treatment exposure anddocumented treatment failures, including therapeutic level with inadequateresponse, clinical intolerance, or affective relapse, were the following: for lithium,28 (90%) of 31 patients experienced prior exposure and 28 (100%) of 28 patientsexperienced prior treatment failure; for valproic acid, 26 (79%) of 31 and 21(81%) of 26; and for carbamazepine, 20 (58%) of 31 and 14 (70%) of 20,respectively.