These findings support the therapeutically favorable conclusion that prior episode counts and treatment delay have little association with morbidity during prophylaxis with mood-stabilizing agents. Comparisons of morbidity during versus before treatment in episodic disorders are misleading because overall morbidity becomes diluted with longer time-at-risk, whereas therapeutic intervention is typically determined by immediately preceding illness.

Key Words: anticonvulsants, bi po lar dis or der, de layed pro phy laxis, kind ling, la tency, lith ium, ma jor af fec tive dis or der, out come, pro phy laxis, re sponse, treat ment P a tients di ag nosed with bi po lar dis or ders (BDs) of ten expe ri ence pro longed la tency from ill ness on set to the start of sus tained, long-term pro phy laxis (1-4). This may rep re sent a par tic u larly crit i cal pe riod in the nat u ral his tory of these disor ders (5-9). A widely con sid ered hy poth e sis is that kindling-like phe nom ena or be hav ioural sen si ti za tion oc curs in BD, as re flected in in creas ingly se vere or more rap idly recur ring ill ness ep i sodes over time (5,6). Of ten cited in sup port of this con cept is ev i dence that in ma jor af fec tive ill nesses the cy cle length (that is, the time from the start of an ep i sode to the start of the next) and the in ter vals of rel a tive wellness be tween acute ep i sodes may un dergo pro gres sive short en ing, par tic ularly with out treat ment (10-12).The kind ling hypoth e sis of pro gres sive wors en ing in major affec tive dis or ders arises from an ani mal model of sec ond arily gen er al ized epi lepsy fol low ing ini tially minor and local ized, exper i men tally induced sei zures (6,13). This phe nom e non is some times taken as a nonhomologous model for mood dis orders. The model sug gests that untreated affec tive ill ness may lead to pathophysiological changes in brain tis sue of untreated patients. Some neuroradiological and post mor tem neuropathological find ings have been inter preted as sup porting this hypoth e sis. They include struc tural changes in brain imag ing and post mor tem neuropathological changes in the brain tis sue of BD patients, as well as sug ges tions that mood sta bi liz ers may pre vent or reverse such changes (7,(14)(15)(16) Ob jec tive:To an a lyze new and re viewed find ings to eval u ate re la tions be tween treat ment response and la tency from on set of bi po lar dis or der (BD) to the start of mood-stabilizer pro phy laxis. Method:We an a lyzed our own new data and added find ings from re search re ports iden ti fied by com put er ized search ing.Re sults: We found 11 rel e vant stud ies, in volv ing 1485 adult pa tients di ag nosed pri mar ily with BD. Re ported la tency to pro phy laxis av er aged 9.6 years (SD 1.3), and fol low-up in treat ment av er aged 5.4 years (SD 3.1). Greater ill ness in ten sity and shorter treat ment la tency were closely as so ci ated, re sult ing in a greater ap par ent re duc tion in mor bid ity with ear lier treat ment. However, this find ing was not sus tained af ter cor rec tion for pre treat ment mor bid ity, and treatment la tency did not pre dict mor bid ity dur ing treat ment. There fore, as sess ments based on improve ment with treat ment, or with out cor rec tion for pre treat ment mor bid ity, can be mis lead ing. Con clu sions:Avail able ev i dence does not sup port the pro posal that de layed pro phy laxis may limit re sponse to pro phy lac tic treat ment i...

Treatment in Psychiatry begins with a hypothetical case illustrating a problem in current clinical practice. The authors review current data on prevalence, diagnosis, pathophysiology, and treatment. The article concludes with the authors' treatment recommendations for cases like the one presented.Mr. B is a 34-year-old man with a 13-year history of schizophrenia. His early treatment consisted of brief trials of first-generation antipsychotics, which he refused to take for any significant period of time. He was then started on risperidone at an average of 5 mg/day. Within a few months, he and his mother noticed that he had upper and lower extremity tremor and profound motor restlessness, especially of the legs. These symptoms worsened until Mr. B was taken off risperidone and started on olanzapine, after which the tremor resolved, but the restlessness persisted. Mr. B's discomfort was so severe that he was unable to sit through a 15-minute medication management appointment without getting up and pacing the room. His mother noted that the restlessness lasted throughout the day, relenting only when he slept. Mr. B stated that he could not stay still for more than a few minutes at a time and that he had an irresistible urge to move, which led him to pace the house and neighborhood until the soles of his feet were bleeding. Mr. B's mother also reported that when the restlessness was at its worst, he was extremely irritable, easily agitated, and sometimes violent.

Factors that reliably predict treatment response in bipolar disorder are much needed, particularly since no available treatment routinely affords complete protection from future illness. The number of pretreatment episodes (PTEs) is a proposed predictor, but its value remains uncertain. We therefore reviewed available research on this topic. Based on a computer-assisted search of the literature, we identified 28 reports providing data on response to lithium treatment and on history of past illness. We evaluated their methods and findings to test the hypothesis that greater PTE count predicts inferior clinical response to lithium. Most studies (68%) found no support for the predicted relationship, and those that did or did not find the hypothesized relationship differed nonsignificantly in ratings of overall study quality and individual factors, including study size, previous lithium use, diagnostic criteria, and outcome measures. The concept that PTE count strongly and consistently predicts inferior clinical response to lithium treatment in manic-depressive disorders is not supported by available research, thus adding to emerging uncertainties about the relationship of past history and later course of these often severe, disabling, and life-threatening illnesses.