Memantine Treatment for Obsessive-compulsive Disorder and Generalized Anxiety Disorder
| Status: | Completed |
|---|---|
| Conditions: | Anxiety, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 10/14/2017 |
| Start Date: | May 2005 |
| End Date: | January 2008 |
Differential Efficacy of Memantine for Obsessive-compulsive Disorder vs. Generalized Anxiety Disorder: an Open-label Trial
The objective of this study was to obtain preliminary open-label data on the efficacy and
tolerability of memantine, an anti-glutamatergic medication with a unique pharmacodynamic
profile, in individuals with OCD and individuals with GAD. Because glutamatergic
hyperactivity in frontal and frontal-subcortical circuits may play a role in the symptomatic
expression of OCD, and possibly GAD, agents that reduce glutamatergic neurotransmission
should provide unique anti-stress and anti-obsessional benefits. Memantine is a specific,
uncompetitive antagonist at the NMDA receptor that blocks sustained activation of the NMDA
receptor by high concentrations of glutamate under pathological conditions but rapidly leaves
the NMDA channel upon transient physiological activation by low concentrations of glutamate.
tolerability of memantine, an anti-glutamatergic medication with a unique pharmacodynamic
profile, in individuals with OCD and individuals with GAD. Because glutamatergic
hyperactivity in frontal and frontal-subcortical circuits may play a role in the symptomatic
expression of OCD, and possibly GAD, agents that reduce glutamatergic neurotransmission
should provide unique anti-stress and anti-obsessional benefits. Memantine is a specific,
uncompetitive antagonist at the NMDA receptor that blocks sustained activation of the NMDA
receptor by high concentrations of glutamate under pathological conditions but rapidly leaves
the NMDA channel upon transient physiological activation by low concentrations of glutamate.
Several case reports and an open-label trial have reported efficacy of anti-glutamatergic
medications for the treatment of OCD. In an open-label trial of riluzole, a glutamate release
inhibitor, seven of 13 adult patients with OCD improved, and five were categorized as
treatment responders. Another open trial found riluzole to be effective for four of six
children with treatment-refractory OCD. N-acetylcysteine, an agent that likely attenuates
glutamate neurotransmission, was effective as an augmentation in one patient with OCD. Two
case reports described memantine treatment of OCD. Poyurovsky et al. reported improvement
with memantine augmentation in one patient with treatment resistant OCD, while Pasquini and
Biondi noted improvement in one OCD patient with checking compulsions but not in one with
contamination obsessions. There have been no controlled or open-label trials of memantine in
OCD reported thus far.
Few studies have examined the efficacy of anti-glutamatergic agents in GAD. In an open-label
trial of riluzole treatment in 18 patients with GAD, twelve patients responded and eight
achieved remission. A double-blind, controlled study found that LY354740, a metabotropic
glutamate receptor 2/3 (mGlu2/3) agonist, was significantly more effective than placebo for
GAD. No studies of memantine in GAD have been reported thus far. We hypothesized that
treatment with memantine would result in significant symptom reduction in both OCD and GAD.
medications for the treatment of OCD. In an open-label trial of riluzole, a glutamate release
inhibitor, seven of 13 adult patients with OCD improved, and five were categorized as
treatment responders. Another open trial found riluzole to be effective for four of six
children with treatment-refractory OCD. N-acetylcysteine, an agent that likely attenuates
glutamate neurotransmission, was effective as an augmentation in one patient with OCD. Two
case reports described memantine treatment of OCD. Poyurovsky et al. reported improvement
with memantine augmentation in one patient with treatment resistant OCD, while Pasquini and
Biondi noted improvement in one OCD patient with checking compulsions but not in one with
contamination obsessions. There have been no controlled or open-label trials of memantine in
OCD reported thus far.
Few studies have examined the efficacy of anti-glutamatergic agents in GAD. In an open-label
trial of riluzole treatment in 18 patients with GAD, twelve patients responded and eight
achieved remission. A double-blind, controlled study found that LY354740, a metabotropic
glutamate receptor 2/3 (mGlu2/3) agonist, was significantly more effective than placebo for
GAD. No studies of memantine in GAD have been reported thus far. We hypothesized that
treatment with memantine would result in significant symptom reduction in both OCD and GAD.
Inclusion Criteria:
- The subject is male or female outpatients over age 18 years,
- The subject meets DSM-IV criteria for Generalized Anxiety Disorder or Obsessive
Compulsive Disorder as determined by the MINI.
- Sexually active female patients of childbearing potential must be practicing at least
one or more the following methods of contraception during the study: intrauterine
device (IUD), barrier method in combination with a spermicide, oral/hormonal
contraception or abstinence. Female patients of childbearing potential must have a
negative pregnancy test prior to receiving study drug.
- Written informed consent must be obtained from the subject prior to study
participation.
- The subject is in good medical health or with chronic medical conditions which are
currently stable.
- No current abuse of alcohol or other substance.
- The subject has a total score of 20 or more on the HARS or YBOCS at screening (for GAD
and OCD, respectively)
- The subject has a Clinical Global Impression (CGI) Severity score of 4 or more at
screening.
Exclusion Criteria:
- The subject meets DSM-IV criteria for an Axis I diagnosis (other than GAD or OCD) as
the primary diagnosis (i.e., schizophrenia, mood disorder, psychosis, anorexia
nervosa) as determined by the MINI.
- The subject is clinically judged by the investigator to be at risk for suicide or is
acutely suicidal as objectively measured by the MINI and MSE.
- The subject is clinically judged by the investigator to be at risk for homicide or is
acutely homicidal as objectively measured by the MINI and MSE.
- The subject has a psychiatric condition that would require inpatient, or partial
psychiatric hospitalization.
- Seizure disorders.
- Significant history of medical disease (i.e. cardiovascular, hepatic (e.g. cirrhosis,
hepatitis B or C) renal, gynecological, musculoskeletal, neurological,
gastrointestinal, metabolic, hematological, endocrine, cancer with a metastatic
potential or progressive neurological disorders) which could impair reliable
participation in the trial or necessitate the use of medication not allowed by this
protocol.
- The subject is pregnant, planning to become pregnant, or nursing. If a subject becomes
pregnant, she will be discontinued immediately and followed appropriately.
- Concomitant therapy with another investigational drug, or participation in an
investigational drug study within one month prior to entering this study.
- Current psychotherapeutic treatment except for treatment with Specific Reuptake
Inhibitor (SSRIs) medications which include: Fluoxetine (Prozac), Paroxetine (Paxil),
Sertraline (Zoloft), Luvox (Fluvoxamine), and Citalopram. Potential subjects may
remain on one of the SSRI medications provided that he or she has been on a stable
dose for at least 4 weeks prior to entering this study; this dose remains stable
throughout the remainder of this study; and it can be determined that this medication
is not exacerbating the anxiety symptoms.
- History of poor compliance or in the Investigator's judgment patients any subject
whose treatment as an outpatient would be clinically contraindicated
- The subject has attempted suicide one or more times within the past twelve months
- The subject has a Structured Hamilton Depression Rating Scale (SIGH-D) score above 38
which suggests a moderate to severe clinical level of depressive symptoms
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