Depression, InvolutionalPhase 2NCT00078715
Rapid Antidepressant Effects of Yohimbine in Major Depression
A Phase 2 study testing Yohimbine hydrochloride in people with Depression, Involutional and Major Depresssion, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study examines if Yohimbine, when given during the sleep cycle, will improve symptoms of depression within a matter of hours. Purpose: This study will examine whether the drug yohimbine, given at a specific time during the sleep cycle, produces chemical changes in the brain similar to those that occur with sleep… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Involutional, Major Depresssion
- What is being tested?
- Yohimbine hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Aug 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects, 18 to 65 years of age.
- Female subjects of childbearing potential must be using a medically accepted means of contraception.
- Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
- Subjects must fulfill DSM-IV criteria for Major Depression, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P.
- Subjects must have an initial score of at least 18 on the 21-item HDRS at screen and at baseline of TSD and Study Phase II.
- Subjects with a greater than 25% decrease in the 21-item HDRS total scores between screen and baseline of TSD will be dropped from the study.
Show all 9Show fewer
- Same as above plus:
- Response to total sleep deprivation (40% decrease in the HAM-D6) followed by:
- Depressive relapse (score of at least 18 on the 21-item HDRS and no longer meets response criteria) prior to Study Period II.
Who cannot join
- Subjects with documented uncontrolled hypertension in the 30 days prior to Study Period I, or have a systolic blood pressure greater than or equal to 140 and/or diastolic blood pressure greater than or equal to 90 on 3 or more readings during the drug-free period.
- Apnea/hypopnea index is greater than 15 episodes per minute.
- Presence of psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV.
- Subjects with current DSM-IV diagnosis of generalized anxiety disorder, panic disorder, or posttraumatic stress disorder.
- Subjects with a history of DSM-IV drug or alcohol dependency or abuse (including for nicotine) within the preceding 3 months.
- Female subjects who are either pregnant or nursing.
Show all 19Show fewer
- Serious, unstable illnesses including hepatic, renal gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
- DSM-IV diagnosis of primary sleep disorder.
- Subjects with uncorrected hypothyroidism or hyperthyroidism.
- Subjects with one or more seizures without a clear and resolved etiology.
- Documented history of hypersensitivity or intolerance to yohimbine.
- Treatment with a reversible MAOI within 4 weeks prior to Study Phase II.
- Treatment with fluoxetine within 3 weeks prior to Study Phase II.
- Treatment with any other concomitant medication not allowed 7 days prior to Study Phase II.
- Treatment with clozapine or ECT within 3 months prior to Study Phase I.
- Judged clinically to be at serious suicide risk.
- Previous nonresponse to total sleep deprivation treatment.
- STUDY PHASE II:
- YMRS total score of greater than or equal to 12 within 24 hours of yohimbine administration.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: An Investigation of a Pharmacologic Strategy to Bring About Rapid (Next Day) Antidepressant Effects
This study examines if Yohimbine, when given during the sleep cycle, will improve symptoms of depression within a matter of hours.
Purpose: This study will examine whether the drug yohimbine, given at a specific time during the sleep cycle, produces chemical changes in the brain similar to those that occur with sleep deprivation. It will also see if yohimbine can induce rapid (next day) antidepressant effects in patients with major depression. Total sleep deprivation for 36 hours improves mood in most patients with major depression in a matter of hours, but the response is usually short-lived. Understanding the chemical changes that occur in the body during sleep deprivation may help in the development of a rapidly acting antidepressant.Patients with major depressive disorder between 18 and 65 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, and blood and urine tests. Participants are hospitalized at the NIH Clinical Center for the study, as follows: Drug-free period: Patients are tapered off their anti-depression medications and remain drug-free for 1 week before beginning study phase 1. Study phase 1: Patients undergo sleep deprivation for 36 hours. Those whose depression improves with sleep deprivation initially and then worsens continue to phase 2. The day after sleep deprivation, patients undergo a lumbar puncture (spinal tap). For this test, a local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle. Study phase 2: Patients spend 1 night in the sleep lab. A catheter (plastic tube) is placed in a vein in each arm-one to give yohimbine and the other to draw blood samples. A small monitor cuff is placed on a finger to measure the patient's blood pressure and blood oxygen levels during the night. While asleep, the patient receives a dose of yohimbine or placebo, given over 3 minutes. A lumbar puncture is done the following morning. Patients receive no medications for 6 days, and then the sleep lab procedure is repeated. Patients who received yohimbine in the previous experiment are switched to placebo, and those who were given placebo are switched to yohimbine.
Read the detailed description
Sleep deprivation is one of the only interventions that have consistently been demonstrated to produce rapid antidepressant effects. The mechanisms by which sleep deprivation brings about rapid antidepressant effects remain to be elucidated. It is noteworthy, however, that recent genomic and proteomic studies have shown that acute sleep deprivation rapidly brings about an upregulation of several mediators of neuronal plasticity, most notably CREB and BDNF. Intriguingly, these are the very same molecules that are upregulated by chronic antidepressants, and are believed to underlie the delayed therapeutic effects of most antidepressants. Additional investigation of the regulation of CREB and BDNF by sleep deprivation has revealed that these changes are critically dependent upon the activation of the noradrenergic system. This is particularly noteworthy, since the locus coeruleus (LC) noradrenergic projection is quiescent only during rapid eye movement sleep (REM), when the target tissues display their greatest sensitivity; indeed, the temporal dissociation between the firing of the LC noradrenergic neurons, and the sensitivity of its postsynaptic targets in the cortex may have considerable relevance for the antidepressant effects of sleep deprivation. In this context, biological rhythms have the capacity to temporally dissociate biochemical processes, and imposing a temporal coincidence on normally dissociated events can have striking and unexpected effects. Thus, it is our hypothesis that activating the normally quiescent noradrenergic system during REM sleep (i.e. when its postsynaptic target system displays its greatest sensitivity) will robustly upregulate CREB and BDNF, thereby bringing about a rapid antidepressant effect. We propose to activate the noradrenergic system during REM sleep by infusing an alpha(2) antagonist, yohimbine. Since it is our hypothesis that activating the noradrenergic system during REM sleep will bring about an antidepressant effect by a similar mechanism as sleep deprivation, we will "enrich" our sample with sleep deprivation responders in this pilot study.
Patients, ages 18 to 65 with a diagnosis of major depressive disorder, currently depressed without psychotic features will be recruited into this study. This experimental proof-of-concept study has two Study Phases. Study Phase I consists of total sleep deprivation. Responders to total sleep deprivation who subsequently relapse will enter Study Phase II. Study Phase II is a double-blind crossover administration of either intravenous yohimbine or saline solution during REM sleep.
The specific aim of this study is to assess the efficacy of a single dose of intravenous yohimbine hydrochloride (0.125 mg/kg given over 3 minutes) compared with placebo in improving overall depressive symptomatology when administered during REM sleep.
Our primary hypothesis is that the intravenous use of an alpha(2) antagonist in patients with major depression during REM sleep will activate the LC and thus increase noradrenergic activity during a time when the LC is normally quiescent- namely REM sleep. If the hypothesis that it is the timing of the activation of the noradrenergic system that is crucial in the antidepressant effect of sleep deprivation is correct then an acute antidepressant effect should be observed in patients despite minimal to no disruption of sleep.
Assuming that 10% will drop out of the study, then a minimum of 25 patients is necessary in order to obtain a minimum of 8 patients with major depression who will complete the double-blind crossover phase of the study.
- Conditions
- Depression, Involutional, Major Depresssion
- Being tested
- Yohimbine hydrochloride, Placebo
- Keywords
- Yohimbine, Sleep Deprivation, Depression, Mood Disorder, Fast, Affective Disorder, Rapid Onset, Major Depression, MDD
- Medical subject headings
- Depressive Disorder, Major, Sleep Deprivation, Depression, Mood Disorders, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Yohimbine hydrochlorideDrug
Participants receive yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep.
PlaceboDrug
Participants receive an inactive equivalent of yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep.
| Study group | Role | What they receive |
|---|---|---|
| Yohimbine then Placebo | Experimental | Participants are randomized to receive yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep. After 8 days they receive placebo administered over 3 minutes during REM sleep. Receives: Drug: Yohimbine hydrochloride; Drug: Placebo |
| Placebo then Yohimbine | Experimental | Participants are randomized to receive placebo administered over 3 minutes during REM sleep. After 8 days they receive yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep. Receives: Drug: Yohimbine hydrochloride; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale (6 Items)
The 6 item Hamilton Depression Rating Scale is a measurement of the severity of depression with a range of scores from 0 to 24, where 24 indicates the most severe depression.
Measured: Once per day, where the primary comparison involves an average over the full study after controlling for baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2004 (estimated)
- Study startMar 2004
- Primary completionAug 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Depression, InvolutionalStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Carlos Zarate, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Carlos A Zarate, M.D., Principal investigator, Experimental Therapeutics and Pathophysiology Branch, DIRP, NIMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00078715
- Sponsor's protocol ID
- 040091
- Other IDs
- 04-M-0091
- Status last verified
- Aug 2019
- First submitted
- 4 Mar 2004
- Last updated
- 29 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Duman RS. Synaptic plasticity and mood disorders. Mol Psychiatry. 2002;7 Suppl 1:S29-34. doi: 10.1038/sj.mp.4001016.
PubMed 11986993Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci. 2001 Jan;2(1):24-32. doi: 10.1038/35049004.
PubMed 11253356Cirelli C, Tononi G. Differential expression of plasticity-related genes in waking and sleep and their regulation by the noradrenergic system. J Neurosci. 2000 Dec 15;20(24):9187-94. doi: 10.1523/JNEUROSCI.20-24-09187.2000.
PubMed 11124996Ibrahim L, Duncan W, Luckenbaugh DA, Yuan P, Machado-Vieira R, Zarate CA Jr. Rapid antidepressant changes with sleep deprivation in major depressive disorder are associated with changes in vascular endothelial growth factor (VEGF): a pilot study. Brain Res Bull. 2011 Aug 10;86(1-2):129-33. doi: 10.1016/j.brainresbull.2011.06.003. Epub 2011 Jun 16.
PubMed 21704134
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigation of a Pharmacologic Strategy to Bring About Rapid (Next Day) Antidepressant Effects
- ClinicalTrials.gov ID
- NCT00078715
- Acronym / sponsor ID
- 040091
- Conditions
- Depression, Involutional, Major Depresssion
- Keywords
- Yohimbine, Sleep Deprivation, Depression, Mood Disorder, Fast, Affective Disorder, Rapid Onset, Major Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Mar 2004
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 5 Mar 2004 (estimated)
- Results
- Posted 16 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study examines if Yohimbine, when given during the sleep cycle, will improve symptoms of depression within a matter of hours.
Purpose: This study will examine whether the drug yohimbine, given at a specific time during the sleep cycle, produces chemical changes in the brain similar to those that occur with sleep deprivation. It will also see if yohimbine can induce rapid (next day) antidepressant effects in patients with major depression. Total sleep deprivation for 36 hours improves mood in most patients with major depression in a matter of hours, but the response is usually short-lived. Understanding the chemical changes that occur in the body during sleep deprivation may help in the development of a rapidly acting antidepressant.Patients with major depressive disorder between 18 and 65 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, and blood and urine tests. Participants are hospitalized at the NIH Clinical Center for the study, as follows: Drug-free period: Patients are tapered off their anti-depression medications and remain drug-free for 1 week before beginning study phase 1. Study phase 1: Patients undergo sleep deprivation for 36 hours. Those whose depression improves with sleep deprivation initially and then worsens continue to phase 2. The day after sleep deprivation, patients undergo a lumbar puncture (spinal tap). For this test, a local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle. Study phase 2: Patients spend 1 night in the sleep lab. A catheter (plastic tube) is placed in a vein in each arm-one to give yohimbine and the other to draw blood samples. A small monitor cuff is placed on a finger to measure the patient's blood pressure and blood oxygen levels during the night. While asleep, the patient receives a dose of yohimbine or placebo, given over 3 minutes. A lumbar puncture is done the following morning. Patients receive no medications for 6 days, and then the sleep lab procedure is repeated. Patients who received yohimbine in the previous experiment are switched to placebo, and those who were given placebo are switched to yohimbine.
Detailed description
Sleep deprivation is one of the only interventions that have consistently been demonstrated to produce rapid antidepressant effects. The mechanisms by which sleep deprivation brings about rapid antidepressant effects remain to be elucidated. It is noteworthy, however, that recent genomic and proteomic studies have shown that acute sleep deprivation rapidly brings about an upregulation of several mediators of neuronal plasticity, most notably CREB and BDNF. Intriguingly, these are the very same molecules that are upregulated by chronic antidepressants, and are believed to underlie the delayed therapeutic effects of most antidepressants. Additional investigation of the regulation of CREB and BDNF by sleep deprivation has revealed that these changes are critically dependent upon the activation of the noradrenergic system. This is particularly noteworthy, since the locus coeruleus (LC) noradrenergic projection is quiescent only during rapid eye movement sleep (REM), when the target tissues display their greatest sensitivity; indeed, the temporal dissociation between the firing of the LC noradrenergic neurons, and the sensitivity of its postsynaptic targets in the cortex may have considerable relevance for the antidepressant effects of sleep deprivation. In this context, biological rhythms have the capacity to temporally dissociate biochemical processes, and imposing a temporal coincidence on normally dissociated events can have striking and unexpected effects. Thus, it is our hypothesis that activating the normally quiescent noradrenergic system during REM sleep (i.e. when its postsynaptic target system displays its greatest sensitivity) will robustly upregulate CREB and BDNF, thereby bringing about a rapid antidepressant effect. We propose to activate the noradrenergic system during REM sleep by infusing an alpha(2) antagonist, yohimbine. Since it is our hypothesis that activating the noradrenergic system during REM sleep will bring about an antidepressant effect by a similar mechanism as sleep deprivation, we will "enrich" our sample with sleep deprivation responders in this pilot study.
Patients, ages 18 to 65 with a diagnosis of major depressive disorder, currently depressed without psychotic features will be recruited into this study. This experimental proof-of-concept study has two Study Phases. Study Phase I consists of total sleep deprivation. Responders to total sleep deprivation who subsequently relapse will enter Study Phase II. Study Phase II is a double-blind crossover administration of either intravenous yohimbine or saline solution during REM sleep.
The specific aim of this study is to assess the efficacy of a single dose of intravenous yohimbine hydrochloride (0.125 mg/kg given over 3 minutes) compared with placebo in improving overall depressive symptomatology when administered during REM sleep.
Our primary hypothesis is that the intravenous use of an alpha(2) antagonist in patients with major depression during REM sleep will activate the LC and thus increase noradrenergic activity during a time when the LC is normally quiescent- namely REM sleep. If the hypothesis that it is the timing of the activation of the noradrenergic system that is crucial in the antidepressant effect of sleep deprivation is correct then an acute antidepressant effect should be observed in patients despite minimal to no disruption of sleep.
Assuming that 10% will drop out of the study, then a minimum of 25 patients is necessary in order to obtain a minimum of 8 patients with major depression who will complete the double-blind crossover phase of the study.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Yohimbine then Placebo | Experimental | Drug: Yohimbine hydrochloride, Drug: PlaceboParticipants are randomized to receive yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep. After 8 days they receive placebo administered over 3 minutes during REM sleep. |
| Placebo then Yohimbine | Experimental | Drug: Yohimbine hydrochloride, Drug: PlaceboParticipants are randomized to receive placebo administered over 3 minutes during REM sleep. After 8 days they receive yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female subjects, 18 to 65 years of age.
- Female subjects of childbearing potential must be using a medically accepted means of contraception.
- Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
- Subjects must fulfill DSM-IV criteria for Major Depression, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P.
- Subjects must have an initial score of at least 18 on the 21-item HDRS at screen and at baseline of TSD and Study Phase II.
Key exclusion criteria (19 listed)
- Subjects with documented uncontrolled hypertension in the 30 days prior to Study Period I, or have a systolic blood pressure greater than or equal to 140 and/or diastolic blood pressure greater than or equal to 90 on 3 or more readings during the drug-free period.
- Apnea/hypopnea index is greater than 15 episodes per minute.
- Presence of psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV.
- Subjects with current DSM-IV diagnosis of generalized anxiety disorder, panic disorder, or posttraumatic stress disorder.
- Subjects with a history of DSM-IV drug or alcohol dependency or abuse (including for nicotine) within the preceding 3 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Yohimbine hydrochlorideParticipants receive yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep. | Drug | Placebo then Yohimbine, Yohimbine then Placebo |
| PlaceboParticipants receive an inactive equivalent of yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep. | Drug | Placebo then Yohimbine, Yohimbine then Placebo |
Primary outcome
Hamilton Depression Rating Scale (6 Items)
Time frame: Once per day, where the primary comparison involves an average over the full study after controlling for baseline
The 6 item Hamilton Depression Rating Scale is a measurement of the severity of depression with a range of scores from 0 to 24, where 24 indicates the most severe depression.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11986993Duman RS. Synaptic plasticity and mood disorders. Mol Psychiatry. 2002;7 Suppl 1:S29-34. doi: 10.1038/sj.mp.4001016.
- Background: PubMed 11253356Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci. 2001 Jan;2(1):24-32. doi: 10.1038/35049004.
- Background: PubMed 11124996Cirelli C, Tononi G. Differential expression of plasticity-related genes in waking and sleep and their regulation by the noradrenergic system. J Neurosci. 2000 Dec 15;20(24):9187-94. doi: 10.1523/JNEUROSCI.20-24-09187.2000.
- Derived from this study: PubMed 21704134Ibrahim L, Duncan W, Luckenbaugh DA, Yuan P, Machado-Vieira R, Zarate CA Jr. Rapid antidepressant changes with sleep deprivation in major depressive disorder are associated with changes in vascular endothelial growth factor (VEGF): a pilot study. Brain Res Bull. 2011 Aug 10;86(1-2):129-33. doi: 10.1016/j.brainresbull.2011.06.003. Epub 2011 Jun 16.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos A Zarate, M.D. principal investigator
Experimental Therapeutics and Pathophysiology Branch, DIRP, NIMH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Yohimbine hydrochloride in people with Depression, Involutional and Major Depresssion, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Rating Scale (6 Items) (time frame: Once per day, where the primary comparison involves an average over the full study after controlling for baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00078715, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2019.