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       #Post#: 23--------------------------------------------------
       Experimental Medication Lifts Depression Symptoms in Bipolar
       Disorder W/I HR
   DIR By: Bipolar Girl
       Date: August 31, 2010, 4:07 pm
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       Science Update • August 06, 2010
       Experimental Medication Lifts Depression Symptoms in Bipolar
       Disorder Within an Hour
       People with treatment-resistant bipolar disorder experienced
       relief from symptoms of depression in as little as 40 minutes
       after an intravenous dose of the anesthetic medication ketamine
       in a preliminary study; while the patient group was small, this
       work adds to evidence that compounds in the class to which
       ketamine belongs have potential as rapid and effective
       medications for depression, including bipolar depression. The
       potential for side-effects makes ketamine an impractical drug
       for standard use, but it provides a way to test this approach
       for developing novel treatments that act more rapidly than
       existing ones.
       Background
       Bipolar disorder (BD) is a potentially debilitating illness
       marked by severe swings in mood, energy, and behavior. Episodes
       of depression alternate with spells of mania but depressive
       episodes tend to be more frequent and longer-lasting and the
       depression is difficult to treat. BD is usually treated with
       mood stabilizing medications such as lithium, valproate,
       carbamazepine or other medications with the goal of preventing
       mood episode relapse. Antidepressant medications are often used
       in addition to a mood stabilizer for depressive episodes, but
       antidepressants typically take weeks to have an effect and many
       patients do not respond adequately to existing medications.
       Previous research has suggested that a disruption of signaling
       between neurons involving the neurotransmitter glutamate is
       likely to play a role in depression. The anesthetic medication
       ketamine shuts down one class of receptor for glutamate (NMDA
       receptors).
       This Study
       Eighteen people with BD participated in this study of ketamine.
       All received maintenance treatment with a mood stabilizer
       medication during the study. All had previously been
       unsuccessfully treated with at least one antidepressant
       medication and a mood stabilizer; the average number of
       medications they had tried unsuccessfully was seven.
       In the first phase of the study, each person was randomly
       assigned to receive a single dose of either intravenous ketamine
       or placebo (saline). After two weeks, treatment was switched, so
       those initially receiving ketamine received placebo, and vice
       versa. Neither patients nor those treating them were told
       whether they were receiving ketamine or placebo. Investigators
       used standard surveys of depression symptoms to assess the
       effect of medication.
       Within 40 minutes, 9 of 16 (56 percent) patients receiving
       ketamine had at least a 50 percent reduction in symptoms, and 2
       of 16 (13 percent) became nearly symptom-free. The response to
       ketamine lasted an average of about a week. By contrast, no
       patients receiving placebo had declines in symptoms close to the
       magnitude seen with ketamine within the first 3 days.
       Significance
       In this study, carried out by scientists Nancy Diazgranados,
       Carlos Zarate, Jr., and colleagues at the Experimental
       Therapeutics & Pathophysiology Branch of NIMH's intramural
       research program, a single intravenous dose of ketamine brought
       relief from depression in severely treatment resistant patients
       with BD, in over half of them within 40 minutes. This study
       supports a previous one by the same group in which they also
       found a rapid antidepressant effect in patients with
       treatment-resistant major depression (unipolar). (NIMH press
       release, August 7, 2006). The authors note that the rapid
       antidepressant response observed in these two different
       disorders (major depressive disorder and bipolar disorder)
       highlights the importance of the NMDA receptor in developing
       treatments with a rapid onset of action.
       The work adds to the evidence of the potential of medications
       targeting the glutamate system for rapid relief from depression,
       even in cases of people who have failed to respond to other
       existing therapies. Rapid and effective treatment of depression
       is an urgent public health need. BD can be disabling—nearly all
       the patients in this study were unemployed as a result of the
       severity of their illness. BD is among the psychiatric disorders
       with the highest risk of suicide.
       Continuing research is focusing on developing NMDA-targeting
       medications that are suitable for clinical use; and
       investigating the use of this class of drugs for long-term
       maintenance of the rapid antidepressant effect seen in this
       study.
       Reference
       Diazgranados, N., Ibrahim, L., Brutsche, N.E., Newberg, A.,
       Kronstein, P., Khalife, S., Kammerer, W. A., Quezado, Z.,
       Luckenbaugh, D.A., Salvadore, G., Machado-Vieira, R., Manji,
       H.K., and Zarate, C. A randomized add-on trial of an
       N-methyl-D-aspartate antagonist in treatment-resistant bipolar
       depression. Archives of General Psychiatry 2010;67(8):793-802.
       For information on this study and other research conducted at
       NIMH please see
  HTML http://patientinfo.nimh.nih.gov/
       or email:
       nimhcore@mail.nih.gov, telephone 301-496-5645.
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