Switching From an SSRI to Tiagabine(GABITRIL) in Order to Alleviate SSRI Induced Sexual Dysfunction
Condition: Anxiety; Sexual Dysfunction
MeSH terms: Anxiety Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      Anxious patients are now treated with Selective Serotonin Reuptake Inhibitor medications
      (common antidepressants) which elevate serotonin and thus alleviate anxiety. These
      medications have clearly proven efficacy upwards of 70% for many anxiety disorders. In
      regards to tolerability, they have a major problem in that they often produce sexual
      dysfunction in men and women (ie. decreased libido, anorgasmia, impotence) upwards of 30% of
      the time.

      Benzodiazepine anxiolytics are also FDA approved to treat anxiety with equal efficacy and
      greater tolerability (very little, if any sexual dysfunction). They do, however, carry a
      substantial risk for addiction. Tiagabine is a Selective GABA Reuptake Inhibitor (SGRI) that
      is FDA approved to treat certain types of epilepsy. Like benzodiazepines, Tiagabine also
      increases the neurotransmitter, GABA, in the brain and is thought to alleviate anxiety (see
      references below) this way too, but without any addiction risk common to Valium-type drugs.
      The safety profile of Tiagabine is thought to be much safer. Two double blind studies are
      ongoing which are looking at Tiagabine's effectiveness in PTSD and GAD. There are many open
      label studies showing anxiety reduction and many psychiatrists in clinical practice are
      utilizing this agent as an anxiety treatment in an off-label manner.

      This study is designed to evaluate anxious patients who are taking SSRI medication, have had
      a reasonable response, but are experiencing significant sexual side effects which are pushing
      them towards noncompliance and possible relapse into anxiety. 30 subjects (15 men and 15
      women) will be asked to join the study and be placed on Tiagabine as well as their current
      SSRI. Once an acceptable dose of Tiagabine is reached in the first four weeks, the subjects'
      SSRIs will be slowly stopped. Two weeks after enrollment, all subjects will be called in
      order to check for any side effects to the study drug and to insure that each subject is
      titrating to the proper dose of study drug according to the study protocol. An open-label,
      non-placebo prospective 10 week follow up will occur, where the now Tiagabine monotherapy
      subjects will be followed to see primarily if their sexual dysfunction improves and if there
      anxiety remains controlled.
    

Detailed description: 
      This is an open-label (no placebo) study to see if a change from SSRI to Tiagabine may
      alleviate sexual dysfunction while maintaining subject in a non-anxious state. 30 Subjects (
      at least 50% female) will currently be taking a single SSRI for at least 4 weeks and report
      at least a 50% drop in their anxiety severity as a result. They must also report a
      chronological emergence of sexual dysfunction ( decreased sex drive, arousal, lubrication, or
      onset of impotence, anorgasmia or delayed ejaculation) following the SSRI initiation.

      Subjects will complete consenting process and attend a screening visit where they will be
      given a MINI psychiatric diagnostic evaluation to confirm anxiety disorder, be given a
      Hamilton Anxiety and a Hospital Anxiety & Depression Scale evaluation to delineate current
      anxiety level (secondary measure). They will also complete self rated sexual health scales
      such as the ASEX to assess sexual functioning (primary measure). Subjects will undergo a
      brief physical exam and bloodwork will be ordered if the patient has an underlying medical
      condition that warrants this type of medical clearance. The same would hold true if an EKG is
      needed. Neither SSRIs, nor tiagabine warrants blood monitoring or EKGs per the FDA.

      Assuming subject meets eligibility, they will start titrating upwards as tolerated on
      tiagabine and downwards on their SSRI. Titration with Tiagabine is flexible but typically
      starts at the night of Day 1: 4 mg/day (2mg qAm with breakfast and 2mq qHS before bedtime
      with a snack for five days). On day 6: 8mg/day (2mg with breakfast and 6mg before bedtime
      with a snack). Day 13: 12mg/day in split doses: (4mg am with breakfast and 8mg before bedtime
      with a snack). Two weeks after enrollment, all subjects will be called in order to check for
      any side effects to the study drug and to insure that each subject is titrating to the proper
      dose of study drug according to the study protocol. At the discretion of the investigator,
      dosing may be lowered to alleviate side effects. Vist 2 will occur at the end of week 4 when
      all SSRI is off and optimal tiagabine is in place. All scales except MINI will be completed.
      Vist 3 will occur at the end of week 8 and scales will be completed. Visit 4 will be the
      final visit at end of week 14, scales, PE and blood/EKG collected as warranted. The efficacy
      and safety of Tiagabine will be evaluated throughout the treatment period (see flow chart).
      At the end of the study, subjects may opt to continue tiagabine or be titrated back to their
      SSRI. Our team will also liaison with the subject's prescriber to ensure follow up and
      continuity of care after study exit.
    

Intervention name(s): Gaitril
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: anxiety; sexual dysfunction; ssri