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Auvelity May Change How You Think About Depression: NMDA, Sigma-1, Dopamine & Clinical Pearls · Pearls and Prep

• 0:00
  Foreign.
• 0:05
  Welcome
• 0:06
  back,
• 0:06
  my
• 0:06
  friends,
• 0:06
  to
• 0:07
  another
• 0:07
  episode
• 0:07
  of
• 0:07
  Pearls
• 0:08
  and
• 0:08
  prep
• 0:08
  npz
• 0:09
  Here,
• 0:09
  your
• 0:09
  preceptor
• 0:10
  in
• 0:10
  your
• 0:10
  pocket,
• 0:11
  your
• 0:11
  go
• 0:11
  to
• 0:11
  place
• 0:12
  for
• 0:12
  pearls
• 0:13
  that
• 0:13
  prep
• 0:13
  you
• 0:13
  to
• 0:14
  practice.
• 0:14
  Today,
• 0:15
  my
• 0:15
  friends,
• 0:15
  we
• 0:16
  are
• 0:16
  going
• 0:16
  to
• 0:16
  do
• 0:17
  a
• 0:17
  fun
• 0:17
  little
• 0:17
  deep
• 0:18
  dive,
• 0:18
  a
• 0:18
  pearl
• 0:19
  dive
• 0:19
  into
• 0:20
  ovelity.
• 0:21
  A
• 0:22
  very
• 0:22
  fascinating
• 0:23
  antidepressant,
• 0:24
  One
• 0:25
  of
• 0:25
  the
• 0:25
  first
• 0:25
  antidepressants
• 0:26
  in
• 0:26
  the
• 0:26
  last
• 0:27
  30
• 0:27
  years
• 0:28
  to
• 0:28
  be
• 0:28
  FDA
• 0:29
  approved.
• 0:30
  That
• 0:30
  is
• 0:30
  not
• 0:30
  a
• 0:31
  simple
• 0:32
  monoamine
• 0:33
  targeted
• 0:34
  antidepressant.
• 0:35
  Right.
• 0:36
  We're
• 0:36
  not
• 0:36
  just
• 0:36
  dealing
• 0:37
  with
• 0:37
  dopamine
• 0:39
  or
• 0:39
  serotonin
• 0:40
  reuptake
• 0:40
  inhibition.
• 0:41
  This
• 0:41
  is
• 0:41
  entirely
• 0:42
  different.
• 0:42
  We're
• 0:43
  talking
• 0:43
  about
• 0:43
  NMDA
• 0:44
  antagonism
• 0:45
  and
• 0:45
  sigma
• 0:46
  1
• 0:46
  receptor
• 0:47
  agonism.
• 0:47
  So
• 0:48
  it's
• 0:48
  very
• 0:48
  novel.
• 0:49
  It's
• 0:49
  actually
• 0:49
  a
• 0:50
  little
• 0:50
  bit
• 0:50
  quicker
• 0:50
  too,
• 0:51
  which
• 0:51
  makes
• 0:51
  it
• 0:51
  even
• 0:52
  more
• 0:52
  novel.
• 0:53
  So
• 0:53
  without
• 0:53
  further
• 0:53
  ado,
• 0:54
  you
• 0:54
  have
• 0:55
  Sarah
• 0:55
  in
• 0:55
  your
• 0:56
  outpatient
• 0:56
  practice.
• 0:57
  She's
• 0:57
  34.
• 0:58
  She's
• 0:58
  a
• 0:58
  marketing
• 0:59
  manager.
• 1:00
  This
• 1:00
  is
• 1:00
  her
• 1:01
  third
• 1:01
  major
• 1:01
  depressive
• 1:02
  episode
• 1:02
  in
• 1:02
  five
• 1:03
  years.
• 1:03
  Moderately
• 1:04
  severe
• 1:04
  PHQ9
• 1:05
  around
• 1:05
  19.
• 1:06
  She's
• 1:06
  tried
• 1:07
  Zoloft
• 1:07
  twice.
• 1:08
  She
• 1:08
  said
• 1:08
  it
• 1:08
  worked
• 1:09
  okay
• 1:09
  for
• 1:09
  Mood,
• 1:10
  but
• 1:10
  she
• 1:10
  discontinued
• 1:11
  it
• 1:11
  both
• 1:11
  times
• 1:12
  because
• 1:12
  of
• 1:12
  the
• 1:12
  sexual
• 1:13
  dysfunction.
• 1:14
  And
• 1:14
  of
• 1:14
  course
• 1:14
  is
• 1:15
  a
• 1:15
  very
• 1:15
  big
• 1:15
  deal
• 1:15
  breaker.
• 1:16
  She
• 1:16
  also
• 1:17
  gained
• 1:17
  like
• 1:17
  15
• 1:17
  pounds
• 1:18
  on
• 1:18
  it.
• 1:18
  And
• 1:18
  she's
• 1:19
  really
• 1:19
  frustrated.
• 1:19
  She's
• 1:20
  telling
• 1:20
  you,
• 1:20
  hey,
• 1:21
  I
• 1:21
  can't
• 1:21
  keep
• 1:21
  choosing
• 1:22
  between
• 1:22
  being
• 1:22
  depressed
• 1:23
  and
• 1:23
  feeling
• 1:23
  like
• 1:23
  a
• 1:23
  zombie
• 1:24
  who
• 1:25
  can't
• 1:25
  have
• 1:25
  sex.
• 1:25
  It's
• 1:26
  just
• 1:26
  a
• 1:26
  deal
• 1:26
  breaker,
• 1:26
  okay?
• 1:27
  She
• 1:27
  has
• 1:27
  no
• 1:27
  seizure
• 1:28
  history,
• 1:28
  no
• 1:28
  eating
• 1:29
  disorder
• 1:29
  history,
• 1:29
  no
• 1:30
  substance
• 1:30
  use.
• 1:31
  She
• 1:31
  works
• 1:31
  in
• 1:31
  a
• 1:32
  really
• 1:32
  high
• 1:32
  pressure
• 1:33
  role.
• 1:33
  And
• 1:33
  she
• 1:34
  tells
• 1:34
  you,
• 1:34
  look,
• 1:34
  I
• 1:35
  can't
• 1:35
  afford
• 1:36
  to
• 1:36
  wait
• 1:36
  six
• 1:37
  weeks
• 1:37
  to
• 1:37
  feel
• 1:37
  better.
• 1:38
  She's
• 1:39
  barely
• 1:39
  holding
• 1:39
  it
• 1:40
  together,
• 1:40
  okay?
• 1:41
  And
• 1:42
  she's
• 1:42
  not
• 1:42
  acutely
• 1:43
  suicidal,
• 1:44
  but
• 1:44
  she
• 1:44
  does
• 1:44
  have
• 1:44
  passive
• 1:45
  ideation,
• 1:45
  like
• 1:45
  a
• 1:46
  what's
• 1:46
  the
• 1:46
  point
• 1:46
  about
• 1:47
  life?
• 1:47
  And
• 1:48
  she's
• 1:48
  not
• 1:48
  really
• 1:49
  a
• 1:49
  candidate
• 1:49
  for
• 1:50
  esketamine
• 1:51
  because
• 1:51
  there's
• 1:52
  no
• 1:52
  REM
• 1:52
  certified
• 1:53
  clinic
• 1:53
  nearby.
• 1:54
  She
• 1:54
  can't
• 1:54
  take
• 1:55
  two
• 1:55
  hours
• 1:55
  off
• 1:55
  of
• 1:55
  work
• 1:56
  twice
• 1:56
  a
• 1:56
  week.
• 1:57
  And
• 1:57
  so
• 1:58
  that's
• 1:59
  the
• 1:59
  story.
• 1:59
  She's
• 1:59
  not
• 1:59
  on
• 2:00
  any
• 2:00
  major
• 2:00
  medications.
• 2:02
  Now
• 2:02
  this
• 2:02
  is
• 2:03
  a
• 2:03
  really
• 2:03
  juicy
• 2:04
  medication
• 2:04
  and
• 2:04
  a
• 2:05
  really
• 2:05
  juicy
• 2:05
  case
• 2:05
  study
• 2:06
  because
• 2:07
  you
• 2:08
  will
• 2:08
  often
• 2:09
  encounter
• 2:09
  patients
• 2:10
  like
• 2:10
  this
• 2:11
  where
• 2:13
  the
• 2:13
  textbook
• 2:14
  says,
• 2:14
  well,
• 2:14
  try
• 2:15
  an
• 2:15
  Snri,
• 2:15
  right?
• 2:16
  She's
• 2:16
  tried
• 2:16
  Zoloft.
• 2:17
  And
• 2:17
  by
• 2:17
  the
• 2:17
  way,
• 2:18
  why
• 2:18
  does
• 2:18
  she
• 2:18
  try
• 2:18
  it
• 2:19
  twice?
• 2:19
  A
• 2:19
  lot
• 2:19
  of
• 2:19
  patients
• 2:20
  will
• 2:20
  just
• 2:20
  get
• 2:21
  back
• 2:21
  on
• 2:21
  a
• 2:21
  medication
• 2:22
  because
• 2:22
  it
• 2:22
  kind
• 2:22
  of
• 2:22
  worked
• 2:23
  and
• 2:23
  they
• 2:23
  kind
• 2:23
  of
• 2:24
  liked
• 2:24
  it
• 2:24
  enough.
• 2:25
  And
• 2:25
  the
• 2:26
  provider
• 2:26
  is
• 2:26
  like,
• 2:26
  well,
• 2:27
  that's
• 2:27
  kind
• 2:27
  of
• 2:27
  good
• 2:27
  enough.
• 2:28
  I'm
• 2:28
  not
• 2:28
  a
• 2:28
  big
• 2:29
  fan
• 2:29
  of
• 2:29
  that.
• 2:29
  I
• 2:29
  don't
• 2:29
  typically
• 2:30
  like
• 2:30
  to
• 2:30
  retry
• 2:31
  patients
• 2:31
  on
• 2:32
  a
• 2:32
  medication.
• 2:32
  They've
• 2:33
  already.
• 2:33
  They've
• 2:34
  already
• 2:34
  taken.
• 2:34
  Unless
• 2:35
  it
• 2:35
  really
• 2:35
  blew
• 2:36
  them
• 2:36
  away
• 2:36
  and
• 2:37
  it
• 2:37
  really
• 2:37
  worked.
• 2:38
  And
• 2:38
  the
• 2:38
  only
• 2:38
  reason
• 2:39
  they're
• 2:39
  off
• 2:39
  of
• 2:39
  it
• 2:39
  is
• 2:39
  because
• 2:40
  of
• 2:40
  some
• 2:40
  insurance
• 2:41
  lapse
• 2:41
  or,
• 2:41
  or
• 2:41
  they
• 2:41
  moved
• 2:42
  across
• 2:42
  the
• 2:42
  country
• 2:43
  or
• 2:43
  something,
• 2:44
  then
• 2:44
  maybe.
• 2:45
  But
• 2:45
  it's
• 2:46
  gotta
• 2:46
  really
• 2:46
  blow
• 2:46
  a
• 2:46
  patient
• 2:47
  away,
• 2:47
  and
• 2:47
  they've
• 2:47
  gotta
• 2:48
  really
• 2:48
  be
• 2:48
  convinced
• 2:49
  that
• 2:49
  it
• 2:49
  was
• 2:49
  a
• 2:49
  game
• 2:49
  changer
• 2:50
  and
• 2:50
  it
• 2:51
  restored
• 2:51
  their
• 2:51
  functioning.
• 2:52
  And
• 2:52
  then
• 2:52
  I
• 2:52
  think
• 2:53
  the
• 2:53
  two
• 2:53
  of
• 2:54
  us
• 2:54
  will
• 2:54
  say,
• 2:54
  yeah,
• 2:54
  let's
• 2:55
  go
• 2:55
  ahead
• 2:55
  and
• 2:55
  do
• 2:55
  some
• 2:55
  Zoloft
• 2:56
  again.
• 2:56
  But
• 2:57
  a
• 2:57
  lot
• 2:57
  of
• 2:57
  times
• 2:58
  patients
• 2:58
  will
• 2:58
  just
• 2:59
  hint
• 3:00
  at
• 3:00
  going
• 3:00
  back
• 3:01
  to
• 3:01
  a
• 3:01
  medication
• 3:01
  because
• 3:02
  it
• 3:02
  was
• 3:02
  comfortable
• 3:02
  to
• 3:03
  them,
• 3:03
  but
• 3:03
  it
• 3:03
  really
• 3:03
  did
• 3:04
  not
• 3:04
  extinguish
• 3:04
  their
• 3:04
  depression
• 3:05
  or
• 3:05
  their
• 3:05
  anxiety.
• 3:06
  And
• 3:06
  as
• 3:06
  a
• 3:06
  provider,
• 3:07
  you've
• 3:07
  gotta
• 3:07
  really
• 3:08
  dig
• 3:08
  and
• 3:08
  make
• 3:09
  sure
• 3:09
  that
• 3:09
  any
• 3:10
  reversion
• 3:10
  back
• 3:11
  to
• 3:11
  a
• 3:11
  past
• 3:12
  medication
• 3:12
  is
• 3:13
  happening
• 3:13
  for
• 3:13
  good
• 3:13
  reason.
• 3:14
  So
• 3:14
  don't
• 3:14
  be
• 3:14
  satisfied
• 3:15
  with
• 3:16
  just,
• 3:16
  oh,
• 3:17
  well,
• 3:17
  it
• 3:17
  kind
• 3:17
  of
• 3:17
  worked,
• 3:18
  but
• 3:18
  not
• 3:18
  really.
• 3:18
  But
• 3:18
  I'm
• 3:19
  used
• 3:19
  to
• 3:19
  it,
• 3:19
  so
• 3:19
  let's
• 3:19
  go
• 3:20
  back
• 3:20
  on
• 3:20
  it
• 3:20
  because
• 3:20
  it's
• 3:20
  this
• 3:21
  default,
• 3:21
  familiar
• 3:22
  medication.
• 3:22
  Get
• 3:23
  a
• 3:23
  little
• 3:23
  picky
• 3:23
  about
• 3:24
  that
• 3:24
  and
• 3:24
  make
• 3:24
  sure,
• 3:25
  if
• 3:25
  you
• 3:25
  can,
• 3:25
  that
• 3:26
  the
• 3:26
  patient
• 3:26
  was
• 3:26
  in
• 3:27
  remission
• 3:27
  and
• 3:27
  their,
• 3:28
  their
• 3:28
  functioning
• 3:28
  was
• 3:29
  markedly
• 3:29
  restored.
• 3:30
  So
• 3:31
  Sarah's
• 3:31
  been
• 3:31
  on
• 3:32
  Zoloft
• 3:32
  twice,
• 3:33
  but
• 3:33
  she's
• 3:33
  kind
• 3:33
  of
• 3:34
  lighting
• 3:34
  a
• 3:34
  fire
• 3:34
  under
• 3:35
  you
• 3:35
  here,
• 3:35
  saying,
• 3:35
  I
• 3:35
  can't
• 3:36
  wait
• 3:36
  six
• 3:36
  weeks
• 3:36
  to
• 3:36
  feel
• 3:37
  better.
• 3:37
  And,
• 3:37
  and,
• 3:38
  you
• 3:38
  know,
• 3:38
  sexual
• 3:38
  dysfunction's
• 3:39
  an
• 3:39
  issue.
• 3:39
  You
• 3:39
  know,
• 3:40
  weight
• 3:40
  gain
• 3:40
  is
• 3:40
  an
• 3:40
  issue.
• 3:41
  So
• 3:41
  now
• 3:41
  you're
• 3:41
  grasping
• 3:42
  for
• 3:42
  this
• 3:42
  and
• 3:42
  going,
• 3:43
  wait
• 3:43
  a
• 3:43
  minute,
• 3:43
  I
• 3:43
  need
• 3:43
  something
• 3:44
  that
• 3:44
  works
• 3:44
  quickly.
• 3:45
  Now,
• 3:45
  Remeron
• 3:46
  is.
• 3:47
  There
• 3:47
  is
• 3:48
  some
• 3:48
  evidence
• 3:48
  that
• 3:48
  Remeron
• 3:49
  can
• 3:49
  work
• 3:49
  a
• 3:49
  little
• 3:49
  faster,
• 3:50
  but
• 3:50
  she
• 3:50
  told
• 3:51
  you
• 3:51
  that
• 3:51
  weight
• 3:51
  gain
• 3:52
  is
• 3:52
  a
• 3:52
  deal
• 3:52
  breaker.
• 3:53
  You
• 3:53
  can't
• 3:53
  do
• 3:54
  Zoloft
• 3:54
  again.
• 3:55
  She's
• 3:55
  tried
• 3:55
  it
• 3:55
  twice.
• 3:55
  She
• 3:56
  doesn't
• 3:56
  want
• 3:56
  to
• 3:56
  wait
• 3:56
  four
• 3:56
  to
• 3:57
  six
• 3:57
  weeks.
• 3:57
  The
• 3:57
  typical
• 3:58
  onboarding
• 3:58
  for
• 3:58
  major
• 3:59
  depressive
• 3:59
  disorder
• 4:00
  or
• 4:00
  anxiety
• 4:01
  can't
• 4:01
  do
• 4:01
  that.
• 4:01
  So
• 4:02
  this
• 4:02
  is
• 4:02
  a
• 4:02
  perfect
• 4:03
  example
• 4:03
  of
• 4:03
  my
• 4:03
  friends,
• 4:04
  of
• 4:04
  how
• 4:04
  the
• 4:05
  next
• 4:05
  best
• 4:05
  thing
• 4:05
  would
• 4:05
  be,
• 4:06
  well,
• 4:06
  let's
• 4:06
  try
• 4:06
  Effexor.
• 4:07
  But
• 4:07
  she's
• 4:07
  not
• 4:08
  willing
• 4:08
  to
• 4:08
  wait.
• 4:08
  She
• 4:09
  wants
• 4:09
  something
• 4:09
  now.
• 4:09
  Now.
• 4:10
  And
• 4:10
  you
• 4:10
  do
• 4:10
  have
• 4:11
  a
• 4:11
  medication
• 4:12
  in
• 4:12
  your
• 4:12
  toolkit
• 4:13
  that
• 4:13
  can
• 4:13
  get
• 4:13
  her
• 4:14
  more
• 4:14
  immediate
• 4:14
  relief.
• 4:15
  That
• 4:15
  is
• 4:16
  a
• 4:16
  little
• 4:16
  bit
• 4:16
  easy
• 4:16
  on
• 4:17
  the
• 4:17
  sexual
• 4:17
  dysfunction.
• 4:18
  It's
• 4:18
  a
• 4:18
  little
• 4:18
  bit
• 4:18
  easy
• 4:19
  on
• 4:19
  the
• 4:19
  weight
• 4:19
  gain,
• 4:19
  and
• 4:20
  it
• 4:20
  might
• 4:20
  work
• 4:20
  within
• 4:20
  a
• 4:21
  week,
• 4:21
  some
• 4:21
  of
• 4:21
  the
• 4:21
  evidence
• 4:22
  shows,
• 4:22
  and
• 4:23
  it
• 4:23
  might
• 4:23
  just
• 4:23
  be
• 4:24
  the
• 4:24
  right
• 4:24
  thing
• 4:25
  for
• 4:25
  her.
• 4:25
  And
• 4:25
  that
• 4:26
  medication
• 4:26
  would
• 4:26
  be
• 4:27
  a
• 4:27
  velity.
• 4:28
  I
• 4:28
  will
• 4:28
  also
• 4:28
  say
• 4:29
  that
• 4:30
  even
• 4:30
  if
• 4:30
  Sarah
• 4:31
  had
• 4:31
  tried
• 4:32
  SNRIs
• 4:32
  and
• 4:33
  SSRIs
• 4:34
  a
• 4:34
  lot
• 4:34
  of
• 4:34
  times,
• 4:35
  in
• 4:35
  my
• 4:35
  experience,
• 4:36
  patients,
• 4:37
  the
• 4:37
  next
• 4:37
  best
• 4:38
  thing,
• 4:38
  let's
• 4:38
  say
• 4:38
  in
• 4:38
  treatment,
• 4:39
  resistant
• 4:39
  depression
• 4:40
  or
• 4:40
  something,
• 4:40
  would
• 4:41
  be
• 4:41
  esketamine
• 4:42
  or
• 4:42
  would
• 4:42
  be
• 4:43
  TMS
• 4:43
  or
• 4:43
  going
• 4:44
  down
• 4:44
  the
• 4:44
  algorithm
• 4:45
  for
• 4:45
  some
• 4:45
  of
• 4:45
  th
• 4:46
  those
• 4:46
  more
• 4:46
  intense
• 4:47
  treatments.
• 4:47
  But
• 4:48
  so
• 4:48
  often
• 4:48
  patients
• 4:49
  are
• 4:49
  busy.
• 4:49
  They
• 4:49
  can't
• 4:50
  sit
• 4:50
  in
• 4:50
  a
• 4:50
  chair
• 4:51
  five
• 4:51
  days
• 4:51
  a
• 4:51
  week
• 4:51
  for
• 4:52
  35
• 4:52
  minutes
• 4:52
  a
• 4:53
  time.
• 4:54
  You
• 4:54
  know,
• 4:55
  with
• 4:55
  these
• 4:55
  magnetic
• 4:56
  coils
• 4:56
  on
• 4:56
  their
• 4:57
  head,
• 4:57
  they
• 4:57
  can't
• 4:58
  do
• 4:58
  esketamine.
• 4:59
  Two
• 4:59
  hours
• 4:59
  off
• 5:00
  work
• 5:00
  twice
• 5:00
  a
• 5:01
  week.
• 5:01
  It's
• 5:01
  just
• 5:01
  not
• 5:01
  viable.
• 5:01
  Right.
• 5:02
  So
• 5:02
  again,
• 5:02
  a
• 5:02
  huge
• 5:03
  chasm
• 5:04
  between
• 5:04
  what
• 5:04
  we
• 5:04
  should
• 5:05
  do
• 5:05
  in
• 5:05
  the
• 5:05
  textbook
• 5:05
  and
• 5:06
  what
• 5:06
  we
• 5:06
  can
• 5:06
  often
• 5:06
  do
• 5:07
  given
• 5:07
  the
• 5:07
  realities
• 5:07
  of
• 5:08
  insurance
• 5:09
  and
• 5:09
  the
• 5:09
  patient's
• 5:09
  own
• 5:10
  schedule
• 5:10
  and
• 5:10
  your
• 5:10
  schedule
• 5:11
  and
• 5:11
  your
• 5:11
  limitations.
• 5:12
  It's
• 5:13
  all
• 5:14
  pretty
• 5:14
  fascinating
• 5:15
  and
• 5:15
  pretty
• 5:16
  interesting
• 5:16
  because
• 5:17
  you,
• 5:17
  you
• 5:17
  are
• 5:17
  in
• 5:18
  almost
• 5:18
  this
• 5:18
  like,
• 5:18
  checkmate
• 5:19
  posture
• 5:19
  where
• 5:19
  you're
• 5:20
  like,
• 5:20
  wow,
• 5:20
  I,
• 5:20
  I
• 5:20
  know
• 5:21
  what
• 5:21
  I
• 5:21
  need
• 5:21
  to
• 5:21
  do.
• 5:21
  I
• 5:22
  know
• 5:22
  what
• 5:22
  my,
• 5:22
  my
• 5:23
  school
• 5:23
  told
• 5:24
  me
• 5:24
  I
• 5:24
  should
• 5:24
  do,
• 5:24
  my
• 5:24
  professors
• 5:25
  told
• 5:25
  me
• 5:25
  to
• 5:25
  do,
• 5:25
  but
• 5:25
  I
• 5:26
  can't
• 5:26
  do
• 5:26
  it.
• 5:26
  And
• 5:27
  this
• 5:27
  is
• 5:27
  where
• 5:27
  a
• 5:27
  velti.
• 5:28
  A
• 5:28
  veloty
• 5:29
  can
• 5:29
  really
• 5:30
  be
• 5:30
  a
• 5:31
  strong
• 5:31
  tool
• 5:32
  in
• 5:32
  your
• 5:32
  toolkit.
• 5:33
  And
• 5:33
  so
• 5:34
  the
• 5:35
  I,
• 5:35
  I
• 5:36
  have
• 5:36
  used
• 5:36
  it
• 5:36
  on
• 5:37
  occasion
• 5:37
  and
• 5:38
  I
• 5:38
  do
• 5:38
  like
• 5:38
  the
• 5:39
  appeal
• 5:39
  of
• 5:40
  the
• 5:40
  fact
• 5:40
  that
• 5:40
  it
• 5:40
  separated
• 5:41
  from
• 5:41
  placebo
• 5:42
  at
• 5:42
  week
• 5:43
  one.
• 5:44
  And
• 5:45
  sometimes
• 5:45
  I
• 5:46
  find
• 5:46
  that
• 5:46
  this
• 5:46
  is
• 5:47
  the
• 5:47
  next
• 5:47
  best
• 5:47
  thing
• 5:47
  when
• 5:48
  TMS
• 5:49
  or
• 5:49
  ketamine
• 5:50
  is
• 5:50
  just
• 5:51
  not
• 5:51
  viable.
• 5:51
  And
• 5:52
  you've
• 5:52
  got
• 5:52
  to
• 5:52
  do
• 5:52
  something
• 5:52
  novel
• 5:53
  and
• 5:53
  different.
• 5:54
  Reaching
• 5:55
  for
• 5:55
  those
• 5:55
  serotonergic
• 5:56
  like
• 5:56
  modulators
• 5:57
  that
• 5:57
  can
• 5:57
  kind
• 5:58
  of
• 5:58
  fine
• 5:58
  tune.
• 5:58
  The
• 5:58
  serotonin
• 5:59
  response
• 5:59
  is
• 6:00
  good.
• 6:00
  But
• 6:00
  remember,
• 6:01
  you
• 6:01
  might
• 6:01
  have
• 6:01
  to
• 6:02
  wait
• 6:02
  a
• 6:02
  little
• 6:02
  bit
• 6:02
  for
• 6:02
  those
• 6:03
  two.
• 6:03
  There's
• 6:03
  prior
• 6:04
  auths,
• 6:05
  there's
• 6:05
  a
• 6:05
  lot
• 6:05
  of
• 6:05
  potential
• 6:06
  delay.
• 6:06
  Now
• 6:06
  you
• 6:06
  may
• 6:06
  also
• 6:07
  have
• 6:07
  a
• 6:07
  prior
• 6:08
  auth
• 6:08
  delay
• 6:08
  with
• 6:09
  a
• 6:09
  velity.
• 6:10
  That's
• 6:10
  possible
• 6:10
  too.
• 6:11
  So
• 6:11
  again,
• 6:11
  what,
• 6:11
  what
• 6:12
  I
• 6:12
  want
• 6:12
  to
• 6:13
  do
• 6:13
  just
• 6:14
  as
• 6:14
  much
• 6:14
  as
• 6:15
  educate
• 6:15
  you
• 6:16
  and
• 6:16
  empower
• 6:16
  you
• 6:17
  from
• 6:17
  a
• 6:17
  psychopharmacology
• 6:18
  perspective,
• 6:19
  I
• 6:19
  want
• 6:19
  to
• 6:19
  also
• 6:20
  educate
• 6:20
  and
• 6:20
  empower
• 6:20
  you
• 6:21
  about
• 6:21
  what
• 6:21
  happens
• 6:22
  when
• 6:22
  you
• 6:22
  graduate
• 6:22
  and
• 6:23
  you're,
• 6:23
  you're
• 6:23
  on
• 6:23
  the
• 6:24
  ground
• 6:24
  and
• 6:25
  you're
• 6:26
  me,
• 6:26
  you're
• 6:26
  hitting
• 6:27
  these
• 6:27
  realities
• 6:27
  head
• 6:28
  on.
• 6:28
  Right?
• 6:29
  The
• 6:29
  insurance
• 6:29
  limitations,
• 6:31
  the
• 6:31
  limitations
• 6:32
  in
• 6:32
  a
• 6:32
  patient's
• 6:33
  schedule,
• 6:33
  their
• 6:34
  own
• 6:34
  stigma,
• 6:34
  their
• 6:35
  own
• 6:35
  deal
• 6:35
  breakers
• 6:35
  that
• 6:36
  they
• 6:36
  have
• 6:36
  about
• 6:36
  particular
• 6:37
  side
• 6:37
  effect
• 6:37
  profiles.
• 6:38
  A
• 6:38
  lot
• 6:38
  of
• 6:38
  the
• 6:39
  meds
• 6:39
  that
• 6:39
  you
• 6:39
  think
• 6:39
  would
• 6:40
  be
• 6:40
  perfect
• 6:40
  in
• 6:41
  a
• 6:41
  textbook
• 6:41
  are
• 6:42
  going
• 6:42
  to
• 6:42
  be
• 6:42
  struck
• 6:42
  out
• 6:43
  systematically
• 6:43
  within
• 6:44
  your
• 6:44
  interview.
• 6:44
  And
• 6:44
  that's
• 6:45
  when
• 6:45
  things
• 6:45
  get
• 6:45
  kind
• 6:45
  of
• 6:45
  fast
• 6:46
  and
• 6:46
  kind
• 6:46
  of
• 6:46
  intense
• 6:47
  and
• 6:47
  you've
• 6:47
  got
• 6:47
  to
• 6:48
  go,
• 6:48
  oh,
• 6:48
  wait
• 6:48
  a
• 6:48
  minute,
• 6:48
  she
• 6:49
  just
• 6:49
  struck
• 6:49
  out.
• 6:49
  That
• 6:49
  next
• 6:50
  thing
• 6:50
  in
• 6:50
  the
• 6:50
  algorithm
• 6:51
  that
• 6:51
  I
• 6:51
  had,
• 6:51
  oh,
• 6:52
  let's
• 6:52
  do
• 6:52
  an
• 6:52
  snri.
• 6:53
  And
• 6:53
  then
• 6:53
  you
• 6:53
  find
• 6:53
  out,
• 6:54
  oh,
• 6:54
  this
• 6:55
  patient
• 6:55
  has
• 6:55
  tried
• 6:55
  Effexor
• 6:56
  and
• 6:56
  she
• 6:56
  never
• 6:57
  wants
• 6:57
  to
• 6:57
  try
• 6:57
  anything
• 6:57
  like
• 6:58
  that
• 6:58
  again.
• 6:58
  She's
• 6:58
  tried
• 6:59
  Effexor
• 6:59
  and
• 6:59
  Cymbalta.
• 7:00
  And
• 7:00
  now
• 7:01
  you're
• 7:01
  like,
• 7:01
  wow,
• 7:01
  I'm
• 7:02
  really
• 7:02
  struck
• 7:02
  out.
• 7:03
  Two
• 7:03
  SSRIs,
• 7:03
  two
• 7:04
  SNRIs.
• 7:04
  What
• 7:05
  on
• 7:05
  earth
• 7:05
  can
• 7:05
  I
• 7:05
  do
• 7:06
  next?
• 7:06
  You
• 7:06
  talk
• 7:07
  about
• 7:07
  tms.
• 7:07
  Oh,
• 7:08
  I'm
• 7:08
  too
• 7:08
  busy,
• 7:08
  I
• 7:08
  can't
• 7:09
  do
• 7:09
  that.
• 7:09
  And
• 7:09
  so
• 7:09
  you're
• 7:10
  like,
• 7:10
  what
• 7:10
  do
• 7:10
  I
• 7:10
  do
• 7:11
  that
• 7:11
  isn't
• 7:12
  completely
• 7:12
  monotonous
• 7:13
  and
• 7:13
  redundant
• 7:14
  and
• 7:14
  crazy?
• 8:09
  And
• 8:10
  so
• 8:10
  again,
• 8:10
  that's
• 8:11
  when
• 8:11
  you
• 8:11
  could
• 8:11
  potentially
• 8:12
  reach
• 8:12
  for
• 8:12
  a
• 8:13
  Velti.
• 8:13
  And
• 8:14
  so
• 8:14
  I
• 8:14
  think
• 8:15
  it's
• 8:16
  a
• 8:16
  pretty
• 8:16
  neat
• 8:17
  medication.
• 8:18
  Now,
• 8:19
  for
• 8:19
  those
• 8:19
  of
• 8:19
  you
• 8:20
  unaware,
• 8:20
  Ovelity
• 8:21
  is
• 8:21
  a
• 8:22
  combination
• 8:22
  of
• 8:22
  dextromethorphan
• 8:23
  and
• 8:24
  wellbutrin.
• 8:25
  45
• 8:26
  milligrams
• 8:26
  of
• 8:26
  dextromethorphan,
• 8:27
  105
• 8:28
  milligrams
• 8:29
  of
• 8:29
  wellbutrin.
• 8:31
  Okay.
• 8:31
  And
• 8:31
  again,
• 8:32
  it's
• 8:32
  one
• 8:32
  of
• 8:32
  the
• 8:32
  first
• 8:33
  fundamentally
• 8:33
  new
• 8:34
  oral
• 8:34
  antidepressant
• 8:35
  mechanisms
• 8:35
  in
• 8:35
  over
• 8:36
  30
• 8:36
  years.
• 8:37
  Okay.
• 8:38
  And
• 8:38
  we're
• 8:38
  kind
• 8:39
  of
• 8:39
  breaking
• 8:39
  free
• 8:39
  from
• 8:40
  the
• 8:40
  monoamine
• 8:40
  only
• 8:41
  paradigm
• 8:41
  in
• 8:41
  a
• 8:42
  take
• 8:42
  home
• 8:42
  pill.
• 8:42
  And
• 8:43
  we're
• 8:43
  looking
• 8:43
  at
• 8:43
  this
• 8:43
  now
• 8:44
  in
• 8:44
  a
• 8:45
  whole
• 8:45
  new
• 8:45
  paradigm.
• 8:46
  Sigma
• 8:46
  one
• 8:46
  agonism,
• 8:47
  NMDA
• 8:48
  antagonism.
• 8:49
  This
• 8:49
  is
• 8:49
  pretty
• 8:50
  cool.
• 8:50
  And
• 8:50
  it
• 8:50
  also
• 8:50
  does
• 8:51
  have
• 8:51
  a
• 8:51
  SIRT
• 8:53
  inhibition,
• 8:53
  so
• 8:54
  it's
• 8:54
  pretty
• 8:55
  neat
• 8:55
  actually.
• 8:56
  Okay.
• 8:56
  Now
• 8:57
  you've
• 8:57
  probably
• 8:57
  heard
• 8:57
  of
• 8:57
  dextromethorphan.
• 8:58
  Yes,
• 8:59
  it
• 8:59
  is
• 8:59
  a
• 8:59
  cough
• 8:59
  suppressant.
• 9:00
  But
• 9:01
  it
• 9:01
  turns
• 9:01
  out
• 9:01
  it's
• 9:01
  also
• 9:02
  a
• 9:02
  potent
• 9:02
  multi
• 9:03
  target
• 9:04
  CNS
• 9:04
  drug
• 9:05
  that's
• 9:05
  kind
• 9:05
  of
• 9:06
  been
• 9:06
  hiding
• 9:06
  in
• 9:07
  plain
• 9:07
  sight
• 9:07
  for
• 9:07
  decades.
• 9:08
  Okay.
• 9:09
  It's
• 9:09
  a
• 9:09
  little
• 9:09
  like
• 9:10
  ketamine
• 9:10
  in
• 9:10
  that
• 9:10
  it,
• 9:11
  it
• 9:11
  is
• 9:11
  a
• 9:11
  NMDA
• 9:12
  receptor
• 9:12
  antagonist.
• 9:13
  You
• 9:13
  got
• 9:13
  the
• 9:13
  brain
• 9:14
  neuroplasticity
• 9:15
  there,
• 9:15
  which
• 9:15
  is
• 9:16
  vit
• 9:16
  and
• 9:16
  really
• 9:17
  all
• 9:17
  mental
• 9:17
  illnesses,
• 9:18
  but
• 9:18
  you
• 9:18
  can
• 9:18
  imagine
• 9:18
  how
• 9:19
  vital
• 9:19
  it
• 9:19
  is
• 9:19
  in
• 9:19
  depression.
• 9:20
  And
• 9:20
  it
• 9:20
  has
• 9:21
  that
• 9:21
  sigma
• 9:21
  1
• 9:21
  receptor
• 9:22
  agonism,
• 9:22
  which
• 9:23
  is
• 9:23
  neuroprotective.
• 9:24
  It's
• 9:24
  also
• 9:25
  pro
• 9:25
  neuroplasticity
• 9:27
  kind
• 9:27
  of
• 9:27
  leverages
• 9:27
  what
• 9:28
  you
• 9:28
  see
• 9:28
  in
• 9:28
  ketamine.
• 9:29
  So
• 9:29
  this
• 9:29
  is
• 9:29
  different.
• 9:30
  And
• 9:30
  I
• 9:31
  will
• 9:31
  argue
• 9:32
  that,
• 9:32
  or
• 9:32
  not
• 9:33
  just
• 9:33
  me,
• 9:33
  but
• 9:33
  the
• 9:33
  evidence
• 9:34
  suggests
• 9:35
  that,
• 9:35
  that
• 9:35
  Sigma
• 9:36
  1
• 9:36
  agonism
• 9:36
  and
• 9:36
  NMDA
• 9:37
  receptor
• 9:37
  antagonism
• 9:38
  is
• 9:38
  why
• 9:38
  this
• 9:39
  can
• 9:39
  often
• 9:39
  kick
• 9:40
  in
• 9:40
  in
• 9:40
  about
• 9:40
  a
• 9:41
  week
• 9:41
  and
• 9:41
  you're
• 9:41
  not
• 9:41
  waiting
• 9:42
  four
• 9:42
  to
• 9:42
  six
• 9:42
  weeks
• 9:42
  for
• 9:43
  those
• 9:43
  downstream
• 9:44
  serotonergic
• 9:45
  changes
• 9:46
  to
• 9:46
  take
• 9:46
  place
• 9:46
  where
• 9:47
  your
• 9:47
  body's
• 9:47
  like
• 9:47
  habituating
• 9:48
  to
• 9:48
  the
• 9:48
  increase
• 9:49
  in
• 9:49
  serotonin
• 9:50
  tone.
• 9:51
  Now
• 9:51
  it
• 9:52
  does
• 9:52
  inhibit
• 9:53
  the
• 9:53
  reuptake
• 9:54
  of
• 9:54
  the
• 9:55
  serotonin
• 9:56
  back
• 9:57
  into
• 9:57
  the
• 9:57
  synapse,
• 9:58
  which
• 9:58
  is
• 9:58
  cool.
• 9:59
  So
• 9:59
  it
• 9:59
  is
• 10:00
  an
• 10:00
  SSRI
• 10:01
  in
• 10:01
  some
• 10:02
  sense,
• 10:02
  but
• 10:03
  it
• 10:03
  has
• 10:03
  a
• 10:03
  weaker
• 10:04
  affinity
• 10:04
  for
• 10:04
  that,
• 10:05
  which
• 10:05
  is
• 10:05
  kind
• 10:05
  of
• 10:06
  why
• 10:06
  it's
• 10:06
  a
• 10:06
  little
• 10:07
  better
• 10:07
  with
• 10:07
  the
• 10:07
  sexual
• 10:08
  Dysfunction
• 10:08
  and
• 10:08
  the
• 10:09
  emotional
• 10:09
  blunting
• 10:10
  that
• 10:11
  is
• 10:11
  more
• 10:11
  common
• 10:12
  in
• 10:12
  classic
• 10:12
  SSRI
• 10:13
  side
• 10:13
  effects.
• 10:14
  Right.
• 10:14
  So
• 10:14
  if
• 10:14
  you
• 10:15
  have
• 10:15
  patients
• 10:15
  who
• 10:15
  are
• 10:15
  really
• 10:15
  complaining
• 10:16
  about,
• 10:16
  oh,
• 10:16
  I
• 10:16
  don't
• 10:17
  want
• 10:17
  to
• 10:17
  feel
• 10:17
  like
• 10:17
  a
• 10:17
  zombie,
• 10:18
  again,
• 10:18
  which
• 10:18
  Sarah
• 10:19
  is
• 10:19
  complaining
• 10:20
  about,
• 10:20
  or
• 10:20
  I
• 10:20
  don't
• 10:21
  want
• 10:21
  to
• 10:21
  have
• 10:21
  sexual
• 10:21
  dysfunction.
• 10:22
  Well,
• 10:23
  this
• 10:23
  cert,
• 10:24
  a
• 10:24
  serotonin
• 10:25
  transporter
• 10:26
  affinity
• 10:27
  is
• 10:28
  actually
• 10:29
  still
• 10:29
  pretty
• 10:29
  tight.
• 10:30
  It's
• 10:30
  all
• 10:31
  the
• 10:31
  tightest
• 10:31
  thing
• 10:32
  about
• 10:32
  ovality
• 10:33
  is
• 10:33
  its
• 10:34
  CERT
• 10:34
  binding.
• 10:35
  So
• 10:36
  ovelity,
• 10:36
  at
• 10:37
  the
• 10:37
  end
• 10:37
  of
• 10:37
  the
• 10:37
  day,
• 10:38
  of
• 10:38
  all
• 10:38
  of
• 10:38
  its
• 10:38
  affinities,
• 10:39
  receptor
• 10:40
  affinities,
• 10:41
  it
• 10:41
  has
• 10:41
  the
• 10:41
  highest
• 10:41
  affinity
• 10:42
  for
• 10:42
  cert,
• 10:43
  okay?
• 10:43
  For
• 10:44
  serotonin
• 10:44
  reuptake
• 10:45
  inhibition,
• 10:46
  however,
• 10:47
  it's
• 10:48
  by
• 10:48
  orders
• 10:48
  of
• 10:48
  magnitude
• 10:49
  much
• 10:49
  weaker
• 10:50
  than
• 10:50
  like
• 10:51
  Paxil
• 10:51
  or
• 10:51
  Zoloft
• 10:52
  or
• 10:52
  Prozac.
• 10:53
  So
• 10:54
  I
• 10:54
  mean,
• 10:55
  we're
• 10:55
  talking
• 10:55
  like
• 10:55
  10
• 10:55
  to
• 10:56
  100
• 10:56
  times
• 10:56
  weaker
• 10:57
  than
• 10:57
  SSRIs
• 10:58
  at
• 10:58
  SIRT.
• 10:59
  So
• 10:59
  again,
• 10:59
  that's
• 11:00
  why
• 11:00
  you
• 11:00
  don't
• 11:00
  have
• 11:00
  those,
• 11:01
  those
• 11:02
  wild
• 11:02
  side
• 11:02
  effects
• 11:02
  that
• 11:03
  usually
• 11:03
  turn
• 11:03
  a
• 11:03
  lot
• 11:03
  of
• 11:03
  people
• 11:04
  off.
• 11:04
  But
• 11:04
  in
• 11:05
  addition
• 11:05
  to
• 11:06
  the,
• 11:07
  the
• 11:07
  affinity
• 11:07
  for
• 11:07
  sirt,
• 11:08
  that's
• 11:08
  a
• 11:08
  little
• 11:08
  lighter
• 11:09
  and
• 11:09
  a
• 11:09
  little
• 11:09
  easier,
• 11:10
  you
• 11:10
  have
• 11:10
  Sigma
• 11:10
  1
• 11:11
  agonism.
• 11:12
  The
• 11:12
  brain
• 11:12
  is
• 11:12
  more
• 11:12
  protected,
• 11:13
  it
• 11:13
  gets
• 11:14
  more
• 11:14
  plastic.
• 11:15
  Mood
• 11:15
  is
• 11:15
  regulated
• 11:16
  a
• 11:16
  little
• 11:16
  bit.
• 11:17
  Glutamate
• 11:17
  is
• 11:17
  modulated
• 11:18
  a
• 11:18
  little
• 11:18
  better.
• 11:19
  That
• 11:19
  excitatory
• 11:19
  neurotransmitter
• 11:20
  that
• 11:21
  can
• 11:21
  be
• 11:21
  really
• 11:22
  problematic
• 11:22
  in
• 11:23
  depression
• 11:23
  or
• 11:23
  anxiety
• 11:24
  where
• 11:24
  you're
• 11:24
  ruminating
• 11:24
  about
• 11:25
  the
• 11:25
  past
• 11:25
  and
• 11:25
  the
• 11:25
  future.
• 11:26
  So
• 11:26
  now
• 11:26
  you
• 11:26
  have
• 11:27
  Sigma
• 11:27
  1
• 11:27
  agonism,
• 11:28
  you
• 11:28
  have
• 11:28
  NMDA
• 11:29
  receptor
• 11:30
  antagonism.
• 11:30
  So
• 11:31
  again,
• 11:32
  more
• 11:32
  glutamate
• 11:33
  modulation,
• 11:33
  that
• 11:33
  hyperexcitable
• 11:34
  neurotransmitter
• 11:35
  that
• 11:36
  makes
• 11:36
  people
• 11:36
  just
• 11:36
  edgy
• 11:37
  and
• 11:37
  agitated.
• 11:38
  So
• 11:38
  your
• 11:39
  modulating
• 11:39
  that
• 11:39
  it's
• 11:40
  the
• 11:40
  NMDA
• 11:41
  receptor
• 11:41
  stuff
• 11:41
  is
• 11:42
  similar
• 11:42
  to
• 11:42
  ketamine,
• 11:43
  where
• 11:43
  you
• 11:43
  have
• 11:43
  more
• 11:43
  of
• 11:44
  a
• 11:44
  rapid
• 11:44
  antidepressant
• 11:45
  effect.
• 11:46
  Sigma
• 11:46
  1
• 11:46
  is
• 11:47
  protecting
• 11:47
  those
• 11:47
  neurons.
• 11:48
  It
• 11:49
  also,
• 11:49
  we
• 11:49
  went
• 11:50
  over
• 11:50
  this
• 11:50
  in
• 11:50
  a
• 11:50
  previous
• 11:50
  episode,
• 11:51
  but
• 11:51
  Sigma
• 11:51
  1
• 11:52
  has
• 11:52
  been
• 11:52
  shown
• 11:53
  to
• 11:53
  modulate
• 11:53
  the
• 11:54
  inflammatory
• 11:54
  response.
• 11:55
  So
• 11:55
  folks
• 11:55
  with
• 11:55
  an
• 11:56
  inflammatory
• 11:56
  subtype
• 11:57
  of
• 11:57
  depression
• 11:58
  might
• 11:58
  benefit
• 11:59
  from
• 12:00
  that
• 12:00
  sigma
• 12:00
  1
• 12:00
  agonism,
• 12:01
  because
• 12:01
  sigma
• 12:01
  1
• 12:02
  receptors
• 12:02
  sit
• 12:02
  on
• 12:03
  immune
• 12:03
  cells,
• 12:03
  has
• 12:04
  a
• 12:04
  little
• 12:04
  bit
• 12:04
  of
• 12:04
  norepinephrine
• 12:06
  reuptake
• 12:06
  inhibition.
• 12:07
  Not
• 12:08
  as
• 12:08
  strong
• 12:09
  as
• 12:09
  the
• 12:10
  SIRT
• 12:10
  affinity,
• 12:11
  but
• 12:11
  still
• 12:12
  pretty
• 12:12
  cool
• 12:12
  because
• 12:13
  look
• 12:13
  at
• 12:13
  all
• 12:13
  of
• 12:13
  this
• 12:14
  you
• 12:14
  have.
• 12:14
  This
• 12:14
  is
• 12:14
  a
• 12:14
  really
• 12:15
  dynamic
• 12:15
  medication.
• 12:16
  And
• 12:17
  of
• 12:17
  course,
• 12:18
  we're
• 12:18
  just
• 12:18
  talking
• 12:19
  really
• 12:19
  about
• 12:19
  dextromethorphan.
• 12:20
  We
• 12:20
  didn't
• 12:20
  even
• 12:20
  include
• 12:21
  Wellbutrin,
• 12:22
  which
• 12:22
  a
• 12:22
  lot
• 12:22
  of
• 12:22
  you
• 12:23
  guys
• 12:23
  are
• 12:23
  more
• 12:23
  familiar
• 12:24
  with.
• 12:24
  But
• 12:24
  remember,
• 12:25
  ovelity
• 12:25
  is
• 12:26
  a
• 12:26
  combination
• 12:26
  of
• 12:26
  dextromethorphan
• 12:27
  and
• 12:28
  Wellbutrin.
• 12:28
  So
• 12:29
  you
• 12:29
  have
• 12:29
  the
• 12:29
  combination
• 12:29
  of
• 12:30
  this
• 12:30
  NMDA
• 12:30
  sigma
• 12:31
  1
• 12:31
  sirt
• 12:32
  Bam.
• 12:33
  Also
• 12:33
  with
• 12:34
  norepinephrine
• 12:35
  and
• 12:35
  dopamine
• 12:35
  reuptake.
• 12:36
  So
• 12:36
  you
• 12:37
  have
• 12:37
  all
• 12:37
  the
• 12:37
  colors
• 12:37
  of
• 12:38
  the
• 12:38
  rainbow
• 12:38
  here.
• 12:39
  And
• 12:39
  that
• 12:39
  is
• 12:40
  what
• 12:40
  makes
• 12:40
  this
• 12:40
  an
• 12:40
  incredibly
• 12:41
  dynamic
• 12:42
  medication.
• 12:42
  Because
• 12:43
  as
• 12:43
  you
• 12:43
  know,
• 12:44
  especially
• 12:44
  in
• 12:45
  treatment
• 12:46
  resistant
• 12:46
  depression,
• 12:47
  you
• 12:47
  have
• 12:48
  a
• 12:48
  lot
• 12:48
  of
• 12:48
  neurotransmitters
• 12:49
  implicated
• 12:50
  in
• 12:50
  that.
• 12:50
  Right.
• 12:50
  People
• 12:51
  feel
• 12:51
  edgy
• 12:51
  and
• 12:51
  anxious
• 12:52
  and
• 12:52
  sad.
• 12:53
  And
• 12:53
  so
• 12:53
  serotonin
• 12:54
  is
• 12:54
  so
• 12:54
  important
• 12:55
  to,
• 12:56
  to
• 12:57
  modulate
• 12:57
  there
• 12:58
  because
• 12:58
  it
• 12:58
  sort
• 12:58
  of
• 12:58
  attenuates
• 12:59
  or
• 13:00
  softens
• 13:00
  extreme
• 13:01
  emotions.
• 13:02
  But
• 13:02
  you
• 13:02
  also
• 13:02
  need
• 13:02
  dopamine.
• 13:03
  Right.
• 13:03
  A
• 13:03
  lot
• 13:03
  of
• 13:03
  your
• 13:04
  patients
• 13:04
  aren't
• 13:04
  motivated,
• 13:05
  they
• 13:05
  have
• 13:05
  brain
• 13:05
  fog,
• 13:06
  they're
• 13:06
  fatigued,
• 13:07
  they
• 13:07
  don't
• 13:08
  get
• 13:08
  any
• 13:08
  joy
• 13:08
  out
• 13:08
  of
• 13:09
  anything.
• 13:09
  So
• 13:09
  you
• 13:09
  definitely
• 13:10
  want
• 13:10
  to
• 13:10
  pull
• 13:10
  them
• 13:10
  out
• 13:10
  of
• 13:11
  their
• 13:11
  anhedonia
• 13:11
  by
• 13:11
  recruiting
• 13:12
  dopamine.
• 13:13
  Well,
• 13:13
  bam,
• 13:13
  you
• 13:13
  got
• 13:14
  that
• 13:14
  with
• 13:14
  the
• 13:14
  Wellbutrin.
• 13:15
  And
• 13:15
  then
• 13:16
  on
• 13:16
  top
• 13:16
  of
• 13:16
  that,
• 13:17
  you've
• 13:17
  added
• 13:17
  these
• 13:17
  dynamic,
• 13:19
  these
• 13:19
  dynamic
• 13:20
  affinity
• 13:20
  profiles
• 13:21
  with
• 13:21
  NMDA
• 13:21
  and
• 13:22
  Sigma
• 13:22
  1
• 13:22
  where
• 13:23
  it's
• 13:23
  being.
• 13:24
  Where
• 13:24
  the
• 13:25
  effect
• 13:25
  is
• 13:25
  happening
• 13:26
  faster,
• 13:26
  which
• 13:27
  patients
• 13:27
  absolutely
• 13:27
  love.
• 13:28
  Nobody
• 13:28
  likes
• 13:28
  to
• 13:29
  hang
• 13:29
  out
• 13:29
  for
• 13:29
  four
• 13:29
  to
• 13:29
  six
• 13:30
  weeks
• 13:30
  with
• 13:30
  these
• 13:30
  symptoms.
• 13:31
  And
• 13:31
  lo
• 13:32
  and
• 13:32
  behold,
• 13:32
  you
• 13:32
  also
• 13:33
  have
• 13:33
  this
• 13:33
  neuroplasticity,
• 13:34
  which
• 13:34
  is
• 13:35
  so
• 13:35
  important.
• 13:35
  Now
• 13:36
  your
• 13:36
  patients
• 13:36
  in
• 13:36
  psychotherapy,
• 13:37
  they
• 13:38
  can
• 13:38
  leverage
• 13:38
  that
• 13:38
  process
• 13:39
  because
• 13:39
  their
• 13:39
  brain's
• 13:40
  becoming
• 13:40
  more
• 13:40
  neuroplastic.
• 13:41
  It's
• 13:41
  being
• 13:42
  protected
• 13:42
  by
• 13:42
  that
• 13:43
  sigma
• 13:43
  1
• 13:43
  receptor
• 13:44
  from
• 13:44
  an
• 13:44
  inflammatory
• 13:46
  cascade,
• 13:47
  from
• 13:47
  inflammatory
• 13:48
  offenders
• 13:49
  that
• 13:49
  are
• 13:49
  all
• 13:49
  over
• 13:50
  our
• 13:50
  environment,
• 13:51
  toxic
• 13:51
  foods
• 13:52
  and
• 13:52
  polluted
• 13:53
  air.
• 13:53
  And,
• 13:53
  and
• 13:54
  COVID
• 13:54
  19.
• 13:55
  Right.
• 13:55
  All
• 13:55
  of
• 13:55
  those
• 13:56
  are
• 13:56
  being
• 13:56
  protected
• 13:57
  a
• 13:57
  little
• 13:57
  more,
• 13:57
  the
• 13:58
  evidence
• 13:58
  suggests,
• 13:58
  by
• 13:59
  sigma
• 13:59
  1
• 13:59
  receptor
• 14:00
  agonism.
• 14:00
  So
• 14:01
  talk
• 14:01
  about
• 14:01
  a
• 14:02
  super
• 14:03
  dynamic
• 14:03
  medication
• 14:04
  and
• 14:04
  one
• 14:04
  that
• 14:05
  you
• 14:05
  really
• 14:05
  need
• 14:05
  to
• 14:05
  appreciate
• 14:06
  and
• 14:06
  think
• 14:07
  about
• 14:07
  and
• 14:08
  reflect
• 14:08
  about
• 14:09
  in
• 14:09
  your
• 14:09
  toolkit
• 14:10
  if
• 14:10
  you
• 14:10
  need
• 14:10
  it.
• 14:10
  Right?
• 14:11
  Really,
• 14:11
  really
• 14:12
  important.
• 14:13
  Okay.
• 14:14
  So
• 14:14
  I
• 14:14
  love
• 14:15
  it.
• 14:15
  I
• 14:15
  think
• 14:15
  that
• 14:15
  any
• 14:16
  medication
• 14:16
  that
• 14:17
  recruits
• 14:17
  multiple
• 14:18
  neurotransmitters
• 14:19
  and
• 14:19
  multiple
• 14:19
  different
• 14:19
  mechanisms
• 14:21
  is
• 14:21
  very
• 14:21
  useful
• 14:22
  and
• 14:23
  very
• 14:23
  exciting.
• 14:24
  Sigma
• 14:24
  one
• 14:25
  in
• 14:25
  and
• 14:25
  of
• 14:25
  itself
• 14:25
  in
• 14:26
  the
• 14:26
  dextromethorphan
• 14:27
  is
• 14:27
  sort
• 14:27
  of
• 14:27
  a
• 14:27
  Swiss
• 14:28
  army
• 14:28
  knife
• 14:28
  of
• 14:29
  the
• 14:29
  brain.
• 14:30
  It's
• 14:30
  really
• 14:30
  not
• 14:31
  a
• 14:31
  traditional
• 14:31
  neurotransmitter
• 14:32
  receptor
• 14:33
  at
• 14:33
  all.
• 14:34
  It's
• 14:34
  more
• 14:34
  like
• 14:34
  a
• 14:35
  molecular
• 14:35
  chaperone.
• 14:36
  It's
• 14:36
  kind
• 14:36
  of
• 14:36
  like
• 14:36
  a
• 14:37
  helper
• 14:37
  protein.
• 14:38
  Not
• 14:38
  to
• 14:38
  get
• 14:38
  too
• 14:39
  technical,
• 14:39
  but
• 14:39
  it's
• 14:40
  pretty
• 14:40
  neat.
• 14:40
  It
• 14:41
  sits
• 14:41
  at
• 14:41
  the
• 14:41
  junction
• 14:42
  between
• 14:42
  your
• 14:42
  endoplasmic
• 14:43
  reticulum.
• 14:44
  That's
• 14:44
  like
• 14:44
  your
• 14:44
  cell's
• 14:45
  protein
• 14:45
  factory.
• 14:46
  Okay.
• 14:46
  And
• 14:46
  it
• 14:46
  kind
• 14:46
  of
• 14:46
  sits
• 14:47
  in
• 14:47
  between
• 14:48
  the
• 14:49
  endoplasmic
• 14:49
  reticulum
• 14:50
  and
• 14:50
  the
• 14:50
  mitochondria,
• 14:51
  which
• 14:51
  is
• 14:51
  like
• 14:51
  your
• 14:52
  powerhouse.
• 14:52
  Right.
• 14:53
  And
• 14:53
  so
• 14:53
  what
• 14:54
  sigma
• 14:54
  1
• 14:55
  receptors
• 14:56
  do
• 14:57
  is
• 14:58
  they
• 14:58
  kind
• 14:58
  of
• 14:58
  regulate
• 14:59
  the
• 14:59
  calcium
• 14:59
  flow.
• 15:00
  Sigma
• 15:00
  1
• 15:00
  receptors
• 15:01
  kind
• 15:01
  of
• 15:01
  regulate
• 15:02
  that
• 15:02
  calcium
• 15:02
  flow
• 15:03
  between
• 15:03
  the
• 15:04
  endoplasmic
• 15:05
  reticulum
• 15:05
  and
• 15:06
  the
• 15:06
  mitochondria,
• 15:07
  okay?
• 15:07
  Very
• 15:08
  important,
• 15:08
  because
• 15:08
  calcium
• 15:09
  at.
• 15:10
  At
• 15:10
  the
• 15:10
  end
• 15:10
  of
• 15:10
  the
• 15:10
  day
• 15:11
  is
• 15:12
  our.
• 15:12
  The
• 15:12
  neuron's
• 15:13
  internal
• 15:14
  signaling
• 15:14
  currency.
• 15:15
  It's
• 15:15
  kind
• 15:15
  of
• 15:15
  how
• 15:15
  it
• 15:15
  signals,
• 15:16
  right?
• 15:17
  And
• 15:17
  if
• 15:17
  you.
• 15:17
  There's
• 15:17
  too
• 15:18
  much
• 15:18
  calcium,
• 15:19
  it
• 15:19
  kind
• 15:19
  of
• 15:19
  kills
• 15:19
  the
• 15:20
  neurons.
• 15:20
  It's
• 15:20
  more
• 15:20
  excitotoxic.
• 15:22
  If
• 15:22
  there's
• 15:22
  too
• 15:23
  little
• 15:23
  calcium,
• 15:23
  the
• 15:24
  cells
• 15:24
  don't
• 15:24
  really
• 15:24
  communicate
• 15:25
  at
• 15:25
  all.
• 15:25
  And
• 15:25
  so
• 15:26
  Sigma
• 15:26
  1
• 15:26
  kind
• 15:26
  of
• 15:27
  keeps
• 15:27
  that
• 15:27
  imbalance,
• 15:29
  and
• 15:29
  that's
• 15:29
  really,
• 15:30
  really
• 15:30
  cool.
• 15:31
  So
• 15:32
  when
• 15:32
  your
• 15:32
  neuron
• 15:33
  is
• 15:33
  under
• 15:33
  stress,
• 15:34
  Sigma
• 15:34
  1
• 15:34
  will
• 15:34
  actually
• 15:35
  physically
• 15:35
  move
• 15:36
  from
• 15:36
  where
• 15:36
  it
• 15:36
  normally
• 15:37
  sits
• 15:37
  in
• 15:37
  between
• 15:37
  the
• 15:38
  endoplasmic
• 15:38
  reticulum
• 15:39
  and
• 15:39
  mitochondria.
• 15:40
  It'll
• 15:40
  go
• 15:40
  to
• 15:41
  the
• 15:41
  cell
• 15:41
  surface.
• 15:42
  It
• 15:42
  kind
• 15:42
  of
• 15:43
  modulates
• 15:43
  ion
• 15:44
  channels,
• 15:45
  and
• 15:45
  it
• 15:46
  really
• 15:46
  protects
• 15:46
  the
• 15:47
  cell.
• 15:47
  Kind
• 15:47
  of
• 15:47
  like
• 15:47
  a
• 15:48
  firefighter
• 15:48
  that
• 15:49
  sits
• 15:49
  at
• 15:49
  the
• 15:49
  station,
• 15:50
  and
• 15:50
  whenever
• 15:50
  there's
• 15:50
  an
• 15:50
  emergency,
• 15:51
  it
• 15:51
  deploys
• 15:52
  and
• 15:52
  it
• 15:52
  puts
• 15:52
  out
• 15:53
  fires
• 15:53
  like
• 15:54
  inflammation
• 15:54
  and
• 15:55
  oxidative
• 15:55
  damage.
• 15:56
  Very
• 15:56
  important
• 15:56
  because
• 15:57
  we
• 15:58
  all
• 15:58
  know
• 15:58
  that
• 15:58
  there's
• 15:59
  so
• 15:59
  many
• 15:59
  inflammatory
• 16:00
  offenders
• 16:01
  that
• 16:01
  can
• 16:01
  make
• 16:01
  depression
• 16:02
  worse.
• 16:02
  There's
• 16:03
  a
• 16:03
  huge
• 16:03
  degree
• 16:03
  of
• 16:04
  folks
• 16:04
  who
• 16:04
  are
• 16:04
  depressed
• 16:05
  who
• 16:05
  have
• 16:05
  that
• 16:05
  inflammatory
• 16:06
  subtype.
• 16:06
  Sigma
• 16:07
  1
• 16:07
  is
• 16:08
  also
• 16:08
  all
• 16:09
  the
• 16:09
  rage
• 16:09
  when
• 16:09
  it
• 16:10
  comes
• 16:10
  to
• 16:10
  Luvox,
• 16:11
  one
• 16:11
  of
• 16:11
  the
• 16:11
  SSRIs.
• 16:12
  That's
• 16:13
  very
• 16:13
  neat
• 16:13
  because
• 16:13
  it
• 16:14
  is
• 16:14
  the
• 16:14
  most
• 16:14
  potent
• 16:14
  sigma
• 16:15
  1
• 16:15
  receptor
• 16:15
  agonist
• 16:16
  of
• 16:16
  all
• 16:16
  the
• 16:16
  SSRIs
• 16:17
  by
• 16:18
  a
• 16:18
  mile.
• 16:19
  There's
• 16:19
  a
• 16:19
  little
• 16:19
  bit
• 16:19
  in
• 16:19
  Zoloft
• 16:20
  and
• 16:20
  Prozac,
• 16:21
  interestingly
• 16:21
  enough,
• 16:22
  but
• 16:22
  Luvox
• 16:23
  blows
• 16:23
  them
• 16:23
  out
• 16:23
  of
• 16:23
  the
• 16:24
  water.
• 16:24
  And
• 16:25
  dextromethorphan
• 16:26
  is
• 16:26
  another
• 16:27
  one
• 16:27
  that
• 16:27
  is
• 16:28
  just
• 16:28
  really
• 16:29
  neuroprotective
• 16:30
  and
• 16:30
  neuroplastic,
• 16:31
  which
• 16:31
  I
• 16:32
  think
• 16:32
  is,
• 16:33
  again,
• 16:33
  just
• 16:34
  so
• 16:34
  freaking
• 16:35
  awesome.
• 16:35
  Now,
• 16:36
  the
• 16:36
  key
• 16:36
  with
• 16:36
  ovelity
• 16:37
  is
• 16:38
  the
• 16:38
  role
• 16:39
  of
• 16:40
  Wellbutrin
• 16:41
  in
• 16:41
  this,
• 16:42
  okay?
• 16:43
  So
• 16:44
  this
• 16:44
  is
• 16:44
  the
• 16:44
  key
• 16:44
  that
• 16:44
  I
• 16:45
  really
• 16:45
  want
• 16:45
  you
• 16:45
  guys
• 16:46
  to
• 16:46
  focus
• 16:46
  on.
• 16:47
  Now,
• 16:47
  when
• 16:47
  you
• 16:48
  take
• 16:48
  the
• 16:48
  Wellbutrin
• 16:48
  with
• 16:49
  the
• 16:49
  dextromethorphan,
• 16:50
  okay,
• 16:51
  The
• 16:51
  Wellbutrin
• 16:52
  inhibits
• 16:52
  it,
• 16:53
  okay?
• 16:53
  With
• 16:54
  the
• 16:54
  CYP2D6
• 16:57
  enzyme,
• 16:58
  okay?
• 16:58
  Because
• 16:58
  normally
• 16:59
  when
• 16:59
  you
• 16:59
  take
• 16:59
  dextromethorphan,
• 17:01
  it's
• 17:01
  immediately
• 17:02
  converted
• 17:03
  and
• 17:03
  it's
• 17:03
  metabolized
• 17:04
  so
• 17:04
  fast
• 17:04
  that
• 17:05
  it
• 17:05
  really
• 17:05
  doesn't
• 17:05
  do
• 17:05
  anything
• 17:06
  to
• 17:06
  your
• 17:06
  brain,
• 17:06
  the
• 17:07
  dextromethorphan.
• 17:08
  But
• 17:08
  because
• 17:08
  you've
• 17:09
  included
• 17:09
  the
• 17:09
  Wellbutrin,
• 17:10
  it
• 17:10
  inhibits
• 17:12
  the
• 17:12
  enzyme
• 17:13
  that
• 17:13
  normally
• 17:14
  converts
• 17:15
  dextromethorphan
• 17:16
  to
• 17:16
  dextrofan,
• 17:17
  okay?
• 17:18
  So
• 17:18
  it
• 17:18
  inhibits
• 17:18
  that
• 17:19
  process,
• 17:20
  okay?
• 17:21
  And
• 17:21
  it
• 17:21
  makes
• 17:22
  these
• 17:22
  blood
• 17:23
  levels
• 17:23
  therapeutic
• 17:24
  for
• 17:24
  the
• 17:24
  dextromethorphan.
• 17:26
  And
• 17:26
  that's
• 17:26
  where
• 17:26
  you
• 17:27
  get
• 17:27
  the
• 17:27
  sigma
• 17:27
  1
• 17:28
  agonism
• 17:28
  that's
• 17:29
  where
• 17:29
  you
• 17:29
  get
• 17:29
  the
• 17:29
  NMDA
• 17:30
  antagonism,
• 17:31
  the
• 17:31
  SIRT
• 17:32
  inhibition.
• 17:32
  That's
• 17:32
  where
• 17:32
  you
• 17:33
  get
• 17:33
  all
• 17:33
  the
• 17:33
  juicy
• 17:33
  stuff.
• 17:34
  Because
• 17:34
  Wellbutrin
• 17:35
  is
• 17:35
  blocking
• 17:37
  the
• 17:38
  metabolism
• 17:40
  that
• 17:40
  would
• 17:40
  otherwise
• 17:41
  basically
• 17:41
  extinguish
• 17:42
  all
• 17:42
  the
• 17:43
  beneficial
• 17:44
  effects
• 17:44
  of
• 17:44
  dextromethorphan.
• 17:45
  Okay.
• 17:46
  And
• 17:47
  it
• 17:47
  actually
• 17:48
  increases.
• 17:48
  Wellbutrin
• 17:49
  increases
• 17:49
  the
• 17:49
  dextromethorphan
• 17:50
  bioavail
• 17:51
  availability
• 17:52
  in
• 17:52
  a
• 17:52
  dramatic
• 17:54
  fashion.
• 17:55
  Okay?
• 17:55
  So
• 17:56
  now
• 17:56
  you
• 17:56
  have
• 17:56
  like
• 17:56
  four
• 17:57
  distinct
• 17:57
  mechanisms
• 17:58
  in
• 17:58
  one
• 17:58
  pill.
• 17:59
  NMDA
• 18:00
  antagonism,
• 18:01
  Sigma
• 18:01
  1
• 18:01
  agonism,
• 18:02
  serotonin
• 18:03
  and
• 18:03
  norepinephrine
• 18:04
  reuptake
• 18:05
  inhibition
• 18:06
  even
• 18:06
  have
• 18:06
  that
• 18:06
  dopamine
• 18:07
  in
• 18:07
  there,
• 18:07
  right,
• 18:08
  with,
• 18:08
  with
• 18:09
  the
• 18:09
  Wellbutrin.
• 18:09
  So
• 18:10
  it's
• 18:10
  unbelievable
• 18:10
  what
• 18:11
  you
• 18:11
  get
• 18:11
  here.
• 18:11
  It's
• 18:12
  really
• 18:12
  cool.
• 18:13
  Okay.
• 18:14
  And
• 18:15
  the
• 18:15
  evidence
• 18:15
  is
• 18:16
  pretty,
• 18:16
  pretty
• 18:16
  solid,
• 18:17
  right?
• 18:17
  The
• 18:17
  combination
• 18:18
  of
• 18:18
  these
• 18:18
  two
• 18:18
  together
• 18:19
  in
• 18:20
  one
• 18:20
  phase
• 18:21
  two
• 18:21
  trial
• 18:21
  out
• 18:22
  back
• 18:22
  in
• 18:22
  the
• 18:22
  day
• 18:23
  showed
• 18:23
  a
• 18:23
  46.5%
• 18:25
  remission
• 18:25
  rate
• 18:25
  with
• 18:25
  this
• 18:26
  combination,
• 18:26
  as
• 18:26
  opposed
• 18:27
  to
• 18:27
  16%
• 18:28
  with
• 18:28
  Wellbutrin
• 18:29
  alone.
• 18:30
  So
• 18:30
  very,
• 18:31
  very
• 18:32
  neat.
• 18:32
  Now
• 18:32
  remember
• 18:32
  though,
• 18:33
  here's
• 18:33
  the
• 18:33
  key.
• 18:34
  For
• 18:34
  folks
• 18:34
  who
• 18:34
  are
• 18:35
  already
• 18:35
  on
• 18:35
  Wellbutrin,
• 18:36
  let's
• 18:36
  say
• 18:36
  at
• 18:36
  like
• 18:36
  a
• 18:36
  450
• 18:37
  milligram
• 18:37
  XL
• 18:38
  dose,
• 18:38
  this
• 18:39
  is
• 18:39
  not
• 18:39
  really
• 18:39
  a
• 18:39
  replacement.
• 18:40
  You
• 18:40
  gotta
• 18:40
  be
• 18:40
  a
• 18:40
  little
• 18:41
  careful
• 18:41
  with
• 18:41
  that.
• 18:42
  If
• 18:42
  you
• 18:42
  have
• 18:42
  a
• 18:42
  patient
• 18:43
  who's
• 18:43
  doing
• 18:43
  so
• 18:43
  well
• 18:43
  on
• 18:44
  450
• 18:45
  and
• 18:45
  you've
• 18:46
  gotta
• 18:46
  knock
• 18:46
  them
• 18:47
  down
• 18:47
  to
• 18:47
  this
• 18:47
  combination
• 18:48
  dose,
• 18:49
  which
• 18:49
  would
• 18:49
  be
• 18:50
  like
• 18:51
  210
• 18:51
  milligrams
• 18:52
  of
• 18:52
  Wellbutrin
• 18:53
  at
• 18:53
  the
• 18:53
  full
• 18:53
  dose.
• 18:54
  It's.
• 18:55
  It
• 18:55
  might
• 18:55
  cut
• 18:56
  your
• 18:56
  patient's
• 18:56
  legs
• 18:57
  off
• 18:57
  a
• 18:57
  bit
• 18:57
  because
• 18:57
  they're
• 18:58
  used
• 18:58
  to
• 18:58
  the
• 18:58
  450.
• 18:59
  You
• 18:59
  don't
• 18:59
  really
• 18:59
  want
• 19:00
  to
• 19:00
  do
• 19:00
  this
• 19:00
  in
• 19:00
  a
• 19:00
  patient
• 19:01
  who's,
• 19:01
  who's
• 19:02
  on
• 19:02
  cloud
• 19:02
  nine
• 19:02
  at
• 19:03
  450
• 19:03
  milligrams
• 19:04
  of
• 19:04
  Wellbutrin.
• 19:04
  This
• 19:04
  is
• 19:04
  good
• 19:05
  for
• 19:05
  somebody
• 19:05
  who's
• 19:06
  already
• 19:06
  off
• 19:06
  their
• 19:06
  antidepressants.
• 19:07
  You
• 19:07
  don't
• 19:08
  have
• 19:08
  to
• 19:08
  worry
• 19:08
  about
• 19:08
  serotonin
• 19:09
  syndrome
• 19:09
  risk
• 19:09
  as
• 19:09
  much.
• 19:10
  And
• 19:11
  you
• 19:11
  can
• 19:11
  kind
• 19:11
  of
• 19:12
  clean
• 19:12
  slate,
• 19:12
  get
• 19:13
  this
• 19:13
  titrated
• 19:13
  up
• 19:14
  and
• 19:15
  get
• 19:15
  them
• 19:15
  to
• 19:16
  a
• 19:16
  Wellbutrin
• 19:17
  dose
• 19:17
  eventually
• 19:18
  of
• 19:18
  210
• 19:19
  milligrams
• 19:20
  a
• 19:20
  day
• 19:21
  in
• 19:21
  combination
• 19:21
  of
• 19:22
  your
• 19:22
  avail
• 19:23
  with
• 19:23
  your,
• 19:23
  with
• 19:23
  your
• 19:23
  dextromethorphan
• 19:24
  component.
• 19:25
  Okay.
• 19:26
  So
• 19:27
  very
• 19:27
  important
• 19:28
  now.
• 19:29
  I
• 19:30
  absolutely
• 19:30
  love
• 19:31
  this.
• 19:31
  We
• 19:31
  did
• 19:31
  talk
• 19:31
  a
• 19:31
  little
• 19:32
  bit
• 19:32
  about
• 19:32
  serotonin
• 19:33
  syndrome.
• 19:33
  You've
• 19:34
  always
• 19:34
  got
• 19:34
  to
• 19:34
  watch
• 19:34
  out
• 19:34
  for
• 19:34
  that
• 19:35
  because
• 19:35
  there
• 19:35
  is
• 19:35
  serotonergic
• 19:36
  component
• 19:36
  in
• 19:37
  the
• 19:37
  dextromethorphan,
• 19:38
  especially
• 19:39
  if
• 19:39
  you're
• 19:39
  using
• 19:40
  SSRIs
• 19:41
  with
• 19:41
  TCAs.
• 19:42
  That
• 19:43
  is
• 19:43
  a
• 19:43
  big
• 19:43
  serotonin
• 19:44
  syndrome
• 19:44
  risk.
• 19:45
  But
• 19:46
  you,
• 19:46
  you
• 19:47
  need
• 19:47
  to
• 19:48
  be
• 19:48
  careful
• 19:49
  with
• 19:50
  dextromethorphan.
• 19:52
  With
• 19:52
  SSRIs,
• 19:54
  it
• 19:54
  might
• 19:54
  require
• 19:55
  very
• 19:55
  careful
• 19:56
  monitoring.
• 19:57
  I
• 19:57
  probably
• 19:57
  wouldn't
• 19:58
  use
• 19:58
  them
• 19:58
  together.
• 19:58
  I
• 19:58
  don't
• 19:58
  feel
• 19:59
  comfortable
• 19:59
  using
• 19:59
  them
• 20:00
  together
• 20:00
  personally.
• 20:01
  But
• 20:01
  using
• 20:02
  SSRIs
• 20:04
  with
• 20:04
  ovelity
• 20:05
  would
• 20:06
  definitely
• 20:06
  require
• 20:06
  careful
• 20:07
  monitoring
• 20:07
  of
• 20:07
  serotonin
• 20:08
  syndrome.
• 20:08
  Good
• 20:08
  psychoeducation
• 20:09
  with
• 20:10
  your
• 20:10
  patient
• 20:10
  for
• 20:10
  serotonin
• 20:11
  syndrome.
• 20:12
  And
• 20:12
  so
• 20:12
  just
• 20:13
  be
• 20:13
  very
• 20:13
  mindful
• 20:13
  of
• 20:14
  that.
• 20:14
  Again,
• 20:14
  the
• 20:14
  SIRT
• 20:15
  inhibition
• 20:15
  is
• 20:15
  not
• 20:15
  as
• 20:16
  powerful
• 20:16
  as
• 20:17
  in
• 20:17
  ssri,
• 20:18
  so
• 20:18
  you
• 20:18
  could
• 20:19
  combine
• 20:19
  them,
• 20:19
  but
• 20:20
  it's
• 20:20
  kind
• 20:21
  of
• 20:21
  risque.
• 20:21
  I
• 20:21
  don't
• 20:22
  like
• 20:22
  doing
• 20:22
  it.
• 20:22
  That's
• 20:23
  not
• 20:23
  really
• 20:23
  my
• 20:23
  thing.
• 20:24
  Okay,
• 20:25
  so
• 20:26
  yeah,
• 20:26
  O
• 20:26
  velity,
• 20:27
  ovelity,
• 20:27
  all
• 20:28
  the
• 20:28
  rage.
• 20:28
  Now
• 20:28
  remember,
• 20:29
  this
• 20:29
  is
• 20:29
  not
• 20:29
  really
• 20:30
  for
• 20:30
  treatment
• 20:31
  resistant
• 20:31
  depression.
• 20:32
  It's
• 20:33
  not
• 20:33
  proven
• 20:34
  in
• 20:34
  treatment
• 20:34
  resistant
• 20:35
  depression.
• 20:36
  This
• 20:36
  is
• 20:36
  more
• 20:36
  about
• 20:37
  major
• 20:37
  depression.
• 20:38
  That's
• 20:38
  the
• 20:38
  FDA
• 20:38
  approval.
• 20:39
  Now,
• 20:40
  oftentimes
• 20:40
  I
• 20:40
  do
• 20:40
  find
• 20:41
  myself
• 20:41
  reaching
• 20:41
  for
• 20:42
  this
• 20:42
  in
• 20:42
  treatment
• 20:42
  resistant
• 20:43
  depression
• 20:43
  because
• 20:43
  patients
• 20:44
  can't
• 20:45
  do
• 20:45
  the
• 20:46
  REMS
• 20:46
  enrollment
• 20:47
  or
• 20:47
  they
• 20:47
  don't
• 20:47
  have
• 20:47
  time
• 20:48
  for
• 20:48
  tms.
• 20:48
  So
• 20:49
  functionally,
• 20:50
  de
• 20:50
  facto,
• 20:51
  I
• 20:52
  feel
• 20:52
  like
• 20:52
  this
• 20:52
  is
• 20:53
  often
• 20:53
  a
• 20:53
  treatment
• 20:53
  resistant
• 20:54
  depression
• 20:54
  pathway.
• 20:55
  Not
• 20:56
  because
• 20:56
  it
• 20:56
  is
• 20:56
  in
• 20:56
  the
• 20:56
  textbooks,
• 20:57
  cause
• 20:57
  it's
• 20:57
  not,
• 20:58
  but
• 20:58
  because
• 20:58
  in
• 20:58
  reality,
• 20:59
  your
• 20:59
  patient
• 21:00
  doesn't
• 21:00
  always
• 21:00
  have
• 21:00
  the
• 21:01
  opportunities
• 21:02
  or
• 21:02
  the
• 21:02
  insurance
• 21:03
  to
• 21:03
  go
• 21:03
  down
• 21:03
  the
• 21:03
  full
• 21:03
  algo
• 21:04
  to
• 21:05
  get
• 21:05
  the
• 21:05
  real
• 21:06
  treatment
• 21:06
  resistant
• 21:07
  depressive
• 21:07
  pathway
• 21:08
  going.
• 21:08
  Okay,
• 21:10
  this
• 21:10
  can
• 21:10
  be
• 21:10
  a
• 21:10
  costly
• 21:11
  treatment,
• 21:12
  but
• 21:12
  again,
• 21:13
  it.
• 21:13
  It's
• 21:14
  something
• 21:14
  to
• 21:14
  consider.
• 21:15
  Yeah,
• 21:15
  you
• 21:16
  don't
• 21:16
  have
• 21:16
  the
• 21:16
  weight
• 21:16
  gain
• 21:17
  and
• 21:17
  sexual
• 21:17
  dysfunction.
• 21:18
  People
• 21:19
  can
• 21:19
  often
• 21:19
  get
• 21:19
  pretty
• 21:19
  dizzy
• 21:20
  on
• 21:20
  a
• 21:20
  Velcito.
• 21:21
  They
• 21:21
  can
• 21:21
  get
• 21:21
  nauseous,
• 21:21
  they
• 21:21
  can
• 21:21
  have
• 21:22
  headaches,
• 21:22
  they
• 21:22
  can
• 21:22
  feel
• 21:22
  really
• 21:23
  tired
• 21:23
  and
• 21:23
  have
• 21:23
  dry
• 21:24
  mouth.
• 21:24
  You
• 21:25
  still
• 21:25
  have
• 21:25
  that
• 21:25
  seizure
• 21:26
  risk
• 21:26
  embedded
• 21:27
  because
• 21:27
  Wellbutrin
• 21:28
  is
• 21:28
  still
• 21:28
  on
• 21:28
  board.
• 21:28
  Remember,
• 21:29
  Wellbutrin
• 21:30
  is
• 21:30
  contraindicated
• 21:31
  in
• 21:31
  seizure
• 21:31
  disorders,
• 21:32
  disorders,
• 21:33
  eating
• 21:33
  disorders,
• 21:34
  abrupt
• 21:34
  alcohol
• 21:35
  and
• 21:35
  benzo
• 21:35
  withdrawal.
• 21:36
  So
• 21:36
  you
• 21:36
  gotta
• 21:36
  be
• 21:36
  careful.
• 21:37
  An
• 21:37
  availability
• 21:38
  can
• 21:38
  cause
• 21:38
  false
• 21:39
  positives
• 21:39
  with
• 21:40
  amphetamine.
• 21:40
  So
• 21:41
  like
• 21:41
  I
• 21:42
  always
• 21:42
  say
• 21:42
  in
• 21:42
  all
• 21:42
  these
• 21:43
  podcast
• 21:43
  episodes,
• 21:44
  there's
• 21:44
  always
• 21:44
  trade
• 21:45
  offs.
• 21:45
  Be
• 21:45
  careful,
• 21:46
  you.
• 21:46
  There's
• 21:47
  no
• 21:47
  free
• 21:47
  lunch
• 21:47
  for
• 21:47
  anything.
• 21:48
  There
• 21:49
  is
• 21:49
  an
• 21:49
  elegance
• 21:50
  to
• 21:50
  this.
• 21:50
  There
• 21:51
  is
• 21:51
  a
• 21:52
  very
• 21:53
  concrete
• 21:53
  rationale
• 21:54
  as
• 21:54
  to
• 21:54
  why
• 21:54
  you
• 21:54
  may
• 21:55
  want
• 21:55
  to
• 21:55
  do
• 21:55
  this
• 21:55
  in
• 21:55
  a
• 21:56
  particular
• 21:56
  patient
• 21:56
  at
• 21:56
  a
• 21:57
  particular
• 21:57
  time.
• 21:57
  And
• 21:58
  I
• 21:58
  will
• 21:58
  tell
• 21:58
  you
• 21:58
  all
• 21:58
  now,
• 21:59
  the
• 21:59
  most
• 21:59
  important
• 21:59
  thing
• 22:00
  is
• 22:00
  you
• 22:00
  and
• 22:01
  your
• 22:01
  patient
• 22:01
  don't
• 22:01
  have
• 22:01
  to
• 22:02
  feel
• 22:02
  powerless
• 22:03
  when
• 22:03
  you've
• 22:03
  already
• 22:03
  gone
• 22:04
  through
• 22:04
  an
• 22:04
  SSRI
• 22:05
  and
• 22:05
  an
• 22:05
  snri.
• 22:06
  And
• 22:06
  your
• 22:06
  patients
• 22:08
  want
• 22:08
  to
• 22:08
  wait
• 22:08
  four
• 22:08
  to
• 22:08
  six
• 22:09
  weeks
• 22:09
  and
• 22:09
  wants
• 22:10
  to
• 22:10
  try
• 22:10
  something
• 22:10
  brand
• 22:11
  new.
• 22:11
  And
• 22:12
  you
• 22:12
  also
• 22:12
  want
• 22:12
  to
• 22:12
  recruit
• 22:13
  different
• 22:13
  neurotransmitters
• 22:14
  and
• 22:14
  mechanism
• 22:14
  mechanisms
• 22:15
  of
• 22:15
  action
• 22:15
  to
• 22:16
  get
• 22:16
  them
• 22:16
  unstuck.
• 22:17
  Well,
• 22:17
  then
• 22:17
  you
• 22:17
  have
• 22:18
  more
• 22:18
  than
• 22:19
  enough
• 22:19
  reasons
• 22:19
  to
• 22:20
  pursue.
• 22:20
  Okay,
• 22:21
  and
• 22:21
  you
• 22:21
  have
• 22:22
  a
• 22:22
  lot
• 22:22
  to
• 22:22
  talk
• 22:22
  about
• 22:22
  with
• 22:23
  them,
• 22:23
  with
• 22:23
  your
• 22:23
  patient,
• 22:24
  as
• 22:24
  to
• 22:25
  why
• 22:25
  you
• 22:25
  chose
• 22:25
  it
• 22:26
  and
• 22:26
  the
• 22:26
  neat
• 22:26
  ways
• 22:26
  this
• 22:27
  might
• 22:27
  get
• 22:27
  them
• 22:27
  unstuck.
• 22:28
  And
• 22:29
  understanding
• 22:29
  the
• 22:29
  how
• 22:30
  and
• 22:30
  the
• 22:30
  why
• 22:30
  is
• 22:31
  key,
• 22:31
  my
• 22:31
  friends.
• 22:32
  The
• 22:33
  biggest
• 22:34
  difference
• 22:34
  between
• 22:34
  a
• 22:35
  good
• 22:35
  and
• 22:35
  a
• 22:35
  great
• 22:35
  clinician
• 22:36
  is
• 22:36
  the
• 22:36
  clinician
• 22:37
  who
• 22:37
  understands
• 22:38
  the
• 22:38
  how
• 22:38
  and
• 22:38
  the
• 22:38
  why.
• 22:39
  The
• 22:39
  clinician
• 22:39
  who
• 22:40
  doesn't
• 22:40
  just
• 22:40
  follow
• 22:40
  the
• 22:41
  algos
• 22:42
  and
• 22:42
  just
• 22:42
  prescribes,
• 22:43
  but
• 22:43
  understands
• 22:44
  why
• 22:44
  those
• 22:44
  algos
• 22:45
  exist
• 22:45
  and
• 22:45
  can
• 22:46
  explain
• 22:46
  it
• 22:46
  to
• 22:47
  the
• 22:47
  patient.
• 22:47
  Patients
• 22:48
  can
• 22:48
  smell
• 22:48
  that
• 22:49
  a
• 22:49
  mile
• 22:49
  away.
• 22:50
  I
• 22:50
  built
• 22:50
  a
• 22:50
  whole
• 22:51
  Patreon
• 22:52
  clinical
• 22:52
  library.
• 22:53
  It's
• 22:53
  in
• 22:53
  the
• 22:54
  show
• 22:54
  notes.
• 22:54
  Please
• 22:54
  click
• 22:55
  it
• 22:55
  before
• 22:55
  you
• 22:55
  go
• 22:55
  to
• 22:56
  bed
• 22:56
  tonight.
• 22:56
  Become
• 22:56
  a
• 22:57
  member.
• 22:57
  I
• 22:57
  built
• 22:58
  it
• 22:58
  for
• 22:58
  you.
• 22:58
  I
• 22:58
  built
• 22:59
  it
• 22:59
  for
• 22:59
  me.
• 22:59
  I
• 22:59
  would
• 23:00
  be
• 23:00
  lost.
• 23:00
  I
• 23:00
  am
• 23:01
  genuinely
• 23:01
  a
• 23:02
  terrified
• 23:02
  of
• 23:03
  where
• 23:03
  I
• 23:03
  would
• 23:03
  be
• 23:04
  in
• 23:04
  my
• 23:04
  career
• 23:04
  if
• 23:05
  I
• 23:05
  didn't
• 23:05
  build
• 23:05
  this
• 23:05
  library
• 23:06
  and
• 23:06
  I
• 23:06
  didn't
• 23:06
  have
• 23:06
  it
• 23:07
  as
• 23:07
  a
• 23:07
  reference
• 23:07
  to
• 23:08
  come
• 23:08
  back
• 23:08
  to.
• 23:08
  I'd
• 23:08
  be
• 23:09
  terrified
• 23:09
  about
• 23:09
  who
• 23:10
  I
• 23:10
  would
• 23:10
  be
• 23:10
  as
• 23:10
  a
• 23:10
  clinician
• 23:11
  because
• 23:11
  it's
• 23:11
  so.
• 23:12
  It's
• 23:12
  played
• 23:13
  such
• 23:13
  a
• 23:13
  huge
• 23:13
  role
• 23:14
  in
• 23:14
  pushing
• 23:15
  me
• 23:15
  forward,
• 23:15
  helping
• 23:16
  me
• 23:16
  stay
• 23:16
  with
• 23:16
  the
• 23:17
  evidence
• 23:17
  and
• 23:17
  understanding
• 23:18
  this
• 23:18
  stuff
• 23:19
  on
• 23:19
  a
• 23:19
  really
• 23:19
  concrete
• 23:20
  level.
• 23:20
  It's
• 23:21
  just
• 23:21
  been
• 23:21
  wonderful
• 23:21
  and
• 23:22
  I
• 23:22
  welcome
• 23:22
  you
• 23:23
  to
• 23:23
  become
• 23:23
  a
• 23:24
  member
• 23:24
  with
• 23:24
  me
• 23:24
  and
• 23:25
  with
• 23:25
  our
• 23:25
  community.
• 23:26
  It
• 23:26
  is
• 23:26
  well
• 23:26
  worth
• 23:27
  your
• 23:27
  time.
• 23:28
  So
• 23:28
  go
• 23:28
  to
• 23:28
  the
• 23:28
  show
• 23:28
  notes.
• 23:29
  Become
• 23:29
  a
• 23:29
  member.
• 23:29
  Take
• 23:30
  care
• 23:30
  of
• 23:30
  yourselves
• 23:31
  and
• 23:31
  each
• 23:31
  other.
• 23:31
  Bye
• 23:32
  Bye.