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A Deep Dive into Second Generation Antipsychotic (SGA) Augmentation for Incomplete Response in Major Depression · Pearls and Prep

• 0:00
  Foreign.
• 0:05
  Welcome
• 0:05
  back,
• 0:05
  my
• 0:06
  friends,
• 0:06
  to
• 0:06
  another
• 0:07
  episode
• 0:07
  of
• 0:08
  Pearls
• 0:09
  and
• 0:09
  Prep.
• 0:10
  This
• 0:10
  one
• 0:11
  is
• 0:11
  a
• 0:11
  request
• 0:12
  from
• 0:12
  one
• 0:12
  of
• 0:12
  our
• 0:12
  listeners
• 0:13
  to
• 0:13
  go
• 0:13
  over
• 0:14
  MDD
• 0:16
  SGA
• 0:18
  augmentation.
• 0:19
  What
• 0:19
  do
• 0:20
  we
• 0:20
  do
• 0:20
  when
• 0:21
  we're
• 0:21
  treating
• 0:21
  major
• 0:22
  depression
• 0:22
  and
• 0:23
  we
• 0:23
  have
• 0:23
  an
• 0:23
  incomplete
• 0:24
  response?
• 0:25
  That's
• 0:25
  what
• 0:25
  this
• 0:26
  is
• 0:26
  about.
• 0:26
  And
• 0:26
  we're
• 0:26
  going
• 0:27
  to
• 0:27
  focus
• 0:27
  particularly
• 0:28
  on
• 0:28
  second
• 0:29
  generation
• 0:29
  antipsychotics
• 0:31
  as
• 0:31
  a
• 0:32
  way
• 0:32
  to
• 0:32
  handle
• 0:33
  this
• 0:33
  situation.
• 0:34
  This
• 0:34
  is
• 0:34
  going
• 0:34
  to
• 0:35
  depend
• 0:35
  on
• 0:35
  the
• 0:35
  practitioner
• 0:36
  and
• 0:36
  the
• 0:36
  kind
• 0:37
  of
• 0:37
  practice
• 0:37
  and
• 0:38
  the
• 0:38
  unique
• 0:39
  patient
• 0:39
  presentation.
• 0:40
  However,
• 0:41
  for
• 0:41
  this
• 0:42
  episode's
• 0:42
  sake,
• 0:43
  we're
• 0:43
  going
• 0:43
  to
• 0:43
  talk
• 0:44
  about
• 0:45
  common
• 0:45
  adjuncts
• 0:46
  and
• 0:46
  what
• 0:47
  they
• 0:47
  specifically
• 0:47
  do.
• 0:48
  Right.
• 0:48
  It's
• 0:48
  not
• 0:48
  enough
• 0:49
  in
• 0:49
  our
• 0:49
  education
• 0:50
  to
• 0:50
  just
• 0:50
  say,
• 0:50
  okay,
• 0:51
  what's
• 0:51
  next
• 0:52
  in
• 0:52
  the
• 0:52
  algorithm?
• 0:52
  We're
• 0:52
  going
• 0:53
  to
• 0:53
  add
• 0:53
  Abilify.
• 0:53
  Well,
• 0:54
  why?
• 0:54
  What
• 0:54
  is
• 0:54
  exactly
• 0:55
  happening
• 0:55
  here?
• 0:56
  The
• 0:57
  next
• 0:57
  level
• 0:58
  is
• 0:59
  when
• 0:59
  we
• 0:59
  understand
• 1:00
  the
• 1:00
  why
• 1:01
  behind
• 1:02
  the
• 1:03
  drug
• 1:03
  actions
• 1:04
  so
• 1:05
  that
• 1:05
  we
• 1:05
  can
• 1:05
  explain
• 1:05
  it
• 1:06
  to
• 1:06
  patients
• 1:06
  and
• 1:06
  have
• 1:07
  more
• 1:07
  of
• 1:07
  a
• 1:07
  sense
• 1:07
  of
• 1:08
  agency.
• 1:08
  We
• 1:09
  have
• 1:09
  a
• 1:09
  sense
• 1:10
  of
• 1:10
  fulfillment
• 1:10
  in
• 1:11
  what
• 1:11
  we
• 1:11
  do
• 1:11
  when
• 1:11
  we
• 1:12
  really
• 1:12
  understand
• 1:13
  what
• 1:13
  it
• 1:13
  is
• 1:13
  that
• 1:13
  we're
• 1:14
  doing
• 1:14
  rather
• 1:15
  than,
• 1:15
  well,
• 1:15
  Abilify
• 1:16
  works
• 1:16
  when
• 1:16
  we
• 1:17
  augment.
• 1:17
  Well,
• 1:17
  why
• 1:18
  and
• 1:18
  by
• 1:18
  how
• 1:18
  much,
• 1:19
  and
• 1:19
  what
• 1:19
  are
• 1:19
  the
• 1:20
  reasons
• 1:20
  behind
• 1:20
  this?
• 1:21
  So,
• 1:22
  first
• 1:23
  off,
• 1:23
  my
• 1:23
  friends,
• 1:24
  these
• 1:24
  episodes
• 1:25
  are
• 1:25
  really
• 1:25
  meant
• 1:26
  to
• 1:26
  be
• 1:26
  more
• 1:26
  of
• 1:27
  a
• 1:27
  conversation.
• 1:28
  You
• 1:28
  know,
• 1:28
  I
• 1:28
  try
• 1:28
  not
• 1:29
  to
• 1:29
  make
• 1:29
  this
• 1:29
  like
• 1:29
  a
• 1:30
  dry,
• 1:30
  boring
• 1:31
  farm
• 1:31
  lecture,
• 1:32
  although
• 1:32
  I
• 1:32
  think
• 1:32
  farm
• 1:32
  is
• 1:33
  one
• 1:33
  of
• 1:33
  the
• 1:33
  most
• 1:33
  fascinating,
• 1:34
  or
• 1:34
  psycho
• 1:34
  farm,
• 1:35
  rather,
• 1:35
  is
• 1:36
  one
• 1:36
  of
• 1:36
  the
• 1:36
  most
• 1:36
  fascinating
• 1:37
  subjects
• 1:38
  in
• 1:38
  NP
• 1:38
  school.
• 1:39
  But
• 1:39
  this
• 1:40
  is
• 1:40
  a
• 1:40
  conversation
• 1:41
  and
• 1:41
  I
• 1:41
  want
• 1:41
  us
• 1:41
  to
• 1:41
  enjoy
• 1:42
  it.
• 1:42
  I
• 1:42
  wish
• 1:42
  I
• 1:42
  could
• 1:42
  talk
• 1:43
  to
• 1:43
  each
• 1:43
  of
• 1:43
  you
• 1:44
  like
• 1:44
  you
• 1:44
  were
• 1:44
  in
• 1:45
  the
• 1:45
  room
• 1:45
  with
• 1:45
  me.
• 1:46
  Could
• 1:46
  field
• 1:46
  your
• 1:46
  questions.
• 1:47
  Even
• 1:47
  more
• 1:48
  reason
• 1:48
  for
• 1:48
  you
• 1:48
  to
• 1:48
  email
• 1:49
  me.
• 1:49
  If
• 1:49
  you
• 1:49
  do
• 1:49
  have
• 1:49
  questions,
• 1:50
  I
• 1:50
  would
• 1:50
  love
• 1:50
  to
• 1:50
  take
• 1:50
  them.
• 1:51
  Let's
• 1:51
  get
• 1:51
  into
• 1:51
  this
• 1:52
  and
• 1:52
  have
• 1:52
  a
• 1:52
  conversation.
• 1:53
  So
• 1:54
  here's
• 1:54
  the
• 1:54
  rub,
• 1:55
  my
• 1:55
  friends.
• 1:55
  When
• 1:56
  we
• 1:56
  try
• 1:56
  to
• 1:56
  treat
• 1:57
  depression
• 1:57
  with
• 1:58
  SSRI
• 1:58
  monotherapy
• 1:59
  with
• 2:00
  Prozac
• 2:00
  or
• 2:00
  Zoloft
• 2:01
  or
• 2:01
  Lexapro,
• 2:02
  we're
• 2:02
  looking
• 2:02
  at
• 2:03
  a
• 2:03
  response
• 2:03
  rate
• 2:04
  of
• 2:04
  anywhere
• 2:04
  between
• 2:04
  40
• 2:05
  and
• 2:05
  50%
• 2:06
  in
• 2:06
  these
• 2:06
  medications.
• 2:07
  Okay?
• 2:08
  Not
• 2:08
  terrible.
• 2:09
  We're
• 2:10
  lucky
• 2:10
  to
• 2:10
  have
• 2:10
  anything
• 2:11
  over
• 2:11
  1%.
• 2:11
  I
• 2:12
  mean,
• 2:12
  we're
• 2:12
  blessed
• 2:12
  that
• 2:13
  there
• 2:13
  are
• 2:13
  medications
• 2:13
  that
• 2:13
  can
• 2:14
  halve
• 2:15
  the
• 2:15
  amount
• 2:15
  of
• 2:15
  misery
• 2:15
  we're
• 2:16
  in
• 2:16
  at
• 2:16
  any
• 2:16
  given
• 2:17
  time.
• 2:17
  But
• 2:18
  40
• 2:18
  to
• 2:18
  50%
• 2:19
  is
• 2:19
  not
• 2:20
  necessarily
• 2:20
  the
• 2:20
  best
• 2:21
  odds
• 2:21
  either.
• 2:21
  You
• 2:21
  know,
• 2:22
  if
• 2:22
  you
• 2:22
  were
• 2:22
  bungee
• 2:23
  jumping
• 2:23
  and
• 2:23
  someone
• 2:23
  said
• 2:24
  there's
• 2:24
  a
• 2:24
  40
• 2:25
  to
• 2:25
  50%
• 2:25
  chance
• 2:26
  that
• 2:27
  this
• 2:27
  cord
• 2:27
  is
• 2:27
  gonna
• 2:28
  work
• 2:28
  out
• 2:28
  for
• 2:29
  you,
• 2:29
  you'd
• 2:29
  probably
• 2:29
  never
• 2:30
  go
• 2:30
  bungee
• 2:30
  jumping.
• 2:31
  Okay,
• 2:32
  so
• 2:32
  40
• 2:32
  to
• 2:32
  50%,
• 2:33
  SSRI
• 2:34
  monotherapy,
• 2:35
  remission,
• 2:35
  that's
• 2:36
  a
• 2:36
  full
• 2:36
  recovery
• 2:38
  as
• 2:38
  measured
• 2:39
  by
• 2:40
  various
• 2:40
  outcome
• 2:41
  measures.
• 2:41
  Whether
• 2:41
  it's
• 2:42
  the,
• 2:42
  you
• 2:42
  know,
• 2:42
  HAMD
• 2:43
  or
• 2:43
  PhQ9
• 2:44
  or
• 2:44
  Mad
• 2:45
  RS.
• 2:46
  But
• 2:46
  if
• 2:47
  a
• 2:47
  full
• 2:47
  remission
• 2:47
  of
• 2:48
  symptoms
• 2:48
  is
• 2:48
  usually
• 2:49
  in
• 2:49
  the
• 2:49
  neighborhood
• 2:49
  of
• 2:49
  25
• 2:50
  to
• 2:50
  30%
• 2:51
  with
• 2:51
  SSRIs
• 2:51
  alone.
• 2:53
  So
• 2:53
  now
• 2:53
  we're
• 2:53
  talking
• 2:54
  70%
• 2:56
  of
• 2:56
  patients
• 2:56
  to
• 2:57
  75%
• 2:58
  of
• 2:58
  patients
• 2:58
  are
• 2:58
  not
• 2:58
  hitting
• 2:59
  full
• 2:59
  remission
• 3:00
  with
• 3:00
  SSRIs
• 3:01
  alone.
• 3:01
  So
• 3:02
  we've
• 3:02
  got
• 3:02
  to
• 3:02
  understand,
• 3:02
  well,
• 3:03
  what's
• 3:03
  going
• 3:03
  on
• 3:03
  here
• 3:04
  and
• 3:04
  what
• 3:05
  can
• 3:05
  we
• 3:05
  do
• 3:05
  about
• 3:05
  it?
• 3:06
  And
• 3:06
  in
• 3:06
  comes
• 3:07
  the
• 3:07
  potential
• 3:08
  to
• 3:08
  augment
• 3:08
  with
• 3:09
  second
• 3:09
  generation
• 3:09
  antipsychotics.
• 3:10
  I
• 3:11
  definitely
• 3:11
  depend
• 3:12
  that
• 3:12
  you
• 3:12
  do
• 3:12
  that
• 3:12
  on
• 3:13
  your
• 3:13
  own.
• 3:13
  We
• 3:13
  can
• 3:13
  dedicate
• 3:14
  a
• 3:14
  new
• 3:14
  episode
• 3:14
  to
• 3:14
  that
• 3:15
  in
• 3:15
  the
• 3:15
  future.
• 3:15
  But
• 3:15
  suffice
• 3:16
  it
• 3:16
  to
• 3:16
  say,
• 3:17
  you
• 3:17
  want
• 3:17
  to
• 3:17
  balance
• 3:18
  these
• 3:18
  interventions
• 3:19
  with
• 3:19
  common
• 3:20
  sense
• 3:20
  and
• 3:20
  with
• 3:20
  the
• 3:21
  literature,
• 3:21
  because
• 3:22
  SGAs,
• 3:22
  as
• 3:23
  you
• 3:23
  know,
• 3:23
  can
• 3:23
  cause
• 3:24
  severe
• 3:24
  weight
• 3:25
  gain,
• 3:26
  muscle
• 3:26
  dystonias,
• 3:27
  a
• 3:28
  whole
• 3:28
  host
• 3:28
  of
• 3:28
  very
• 3:28
  potentially
• 3:29
  serious
• 3:29
  side
• 3:29
  effects.
• 3:30
  Right.
• 3:30
  Parkinsonian
• 3:31
  symptoms
• 3:31
  and
• 3:31
  Ms.
• 3:33
  But
• 3:33
  again,
• 3:33
  we're
• 3:33
  not
• 3:33
  going
• 3:33
  to
• 3:34
  go
• 3:34
  into
• 3:34
  that
• 3:34
  too
• 3:34
  much
• 3:35
  today
• 3:36
  when
• 3:36
  we're
• 3:36
  talking
• 3:36
  about
• 3:37
  SGA
• 3:37
  augmentation.
• 3:38
  What
• 3:38
  the
• 3:38
  meta
• 3:39
  analysis
• 3:39
  show,
• 3:40
  the
• 3:40
  literature
• 3:41
  essentially
• 3:41
  shows
• 3:42
  the
• 3:42
  response
• 3:42
  rates
• 3:43
  can
• 3:43
  go
• 3:43
  upwards
• 3:44
  towards
• 3:44
  50
• 3:44
  to
• 3:45
  60%.
• 3:45
  Remission
• 3:46
  rates
• 3:46
  35
• 3:47
  to
• 3:47
  45%.
• 3:47
  So
• 3:48
  considerable
• 3:49
  improvement
• 3:50
  and
• 3:50
  an
• 3:51
  even
• 3:51
  better
• 3:51
  improvement,
• 3:52
  particularly
• 3:53
  with
• 3:53
  Abilify
• 3:54
  specifically.
• 3:54
  Abilify
• 3:55
  tends
• 3:56
  to
• 3:56
  convey
• 3:57
  odds
• 3:57
  ratios
• 3:57
  of
• 3:58
  a
• 3:58
  response
• 3:59
  of
• 3:59
  about
• 3:59
  1.9,
• 4:00
  which
• 4:00
  means
• 4:00
  that
• 4:00
  it
• 4:01
  tends
• 4:01
  to
• 4:01
  have
• 4:01
  a
• 4:02
  almost,
• 4:02
  you
• 4:02
  know,
• 4:03
  90%
• 4:04
  increase
• 4:05
  of
• 4:06
  helping
• 4:06
  that
• 4:07
  patient
• 4:07
  respond.
• 4:08
  90%
• 4:09
  higher
• 4:09
  odds
• 4:10
  than
• 4:10
  placebo
• 4:11
  augmentation.
• 4:12
  Very
• 4:13
  convincing
• 4:14
  numbers
• 4:14
  there.
• 4:14
  And
• 4:15
  we'll
• 4:15
  talk
• 4:15
  about
• 4:15
  why
• 4:15
  Abilify
• 4:16
  is
• 4:17
  kind
• 4:17
  of
• 4:17
  a
• 4:17
  unique
• 4:17
  case.
• 4:18
  There's
• 4:18
  a
• 4:19
  previous
• 4:19
  episode,
• 4:19
  all
• 4:19
  on
• 4:20
  Abilify
• 4:20
  that
• 4:20
  is
• 4:21
  really
• 4:21
  exciting.
• 4:22
  I
• 4:22
  encourage
• 4:23
  you
• 4:23
  all
• 4:23
  to
• 4:24
  subscribe
• 4:24
  and
• 4:25
  and
• 4:25
  check
• 4:25
  more
• 4:25
  of
• 4:26
  our
• 4:26
  stuff
• 4:26
  out.
• 4:26
  The
• 4:27
  remission
• 4:27
  rates
• 4:28
  are
• 4:29
  25
• 4:29
  to
• 4:30
  30%,
• 4:30
  which
• 4:30
  is
• 4:31
  not
• 4:31
  the
• 4:32
  best
• 4:32
  response.
• 4:33
  Rates
• 4:33
  are
• 4:33
  incomplete
• 4:34
  at
• 4:34
  around
• 4:34
  40
• 4:35
  to
• 4:35
  50.
• 4:35
  And
• 4:36
  what
• 4:36
  makes
• 4:36
  this
• 4:37
  episode
• 4:37
  interesting
• 4:37
  is
• 4:38
  that
• 4:38
  we
• 4:38
  delve
• 4:39
  into
• 4:39
  the
• 4:39
  details
• 4:40
  about
• 4:40
  what
• 4:41
  that
• 4:41
  lack
• 4:41
  of
• 4:41
  response
• 4:42
  looks
• 4:43
  like.
• 4:43
  SSRIs
• 4:44
  are
• 4:44
  blunt
• 4:45
  tools.
• 4:45
  So
• 4:45
  when
• 4:45
  you
• 4:46
  start
• 4:46
  an
• 4:46
  SSRI,
• 4:47
  it's
• 4:48
  not
• 4:48
  like
• 4:48
  there's
• 4:48
  one
• 4:49
  serotonin
• 4:49
  receptor
• 4:50
  that
• 4:51
  gets
• 4:52
  activated
• 4:52
  by
• 4:53
  your
• 4:53
  SSRI
• 4:53
  and
• 4:54
  everybody
• 4:54
  goes
• 4:54
  home
• 4:54
  happy.
• 4:55
  It's
• 4:55
  not
• 4:55
  like
• 4:55
  that.
• 4:56
  Right.
• 4:56
  We
• 4:56
  have
• 4:57
  serotonin
• 4:57
  receptors
• 4:58
  in
• 4:58
  various
• 4:58
  parts
• 4:59
  of
• 4:59
  the
• 4:59
  brain
• 4:59
  that
• 4:59
  do
• 5:00
  various
• 5:00
  types
• 5:00
  of
• 5:00
  things.
• 5:01
  We
• 5:01
  have
• 5:01
  serotonin
• 5:02
  receptors
• 5:02
  in
• 5:02
  the
• 5:02
  gut
• 5:03
  that
• 5:03
  can
• 5:03
  influence
• 5:04
  GI
• 5:04
  side
• 5:05
  effects
• 5:05
  that
• 5:05
  we
• 5:05
  don't
• 5:05
  necessarily
• 5:06
  want.
• 5:07
  We
• 5:07
  have
• 5:07
  serotonin
• 5:08
  receptors
• 5:09
  that
• 5:09
  can
• 5:09
  influence
• 5:10
  sexual
• 5:10
  side
• 5:10
  effects
• 5:11
  and
• 5:11
  our
• 5:11
  libido
• 5:12
  and
• 5:12
  they
• 5:12
  can
• 5:13
  lead
• 5:13
  to
• 5:13
  downstream
• 5:14
  dampening
• 5:14
  of
• 5:14
  dopamine,
• 5:15
  which
• 5:15
  can
• 5:15
  cause
• 5:16
  things
• 5:16
  like
• 5:17
  a
• 5:17
  lack
• 5:17
  of
• 5:17
  motivation
• 5:18
  and
• 5:18
  apathy
• 5:19
  the
• 5:19
  first
• 5:19
  step
• 5:20
  when
• 5:20
  we
• 5:20
  think
• 5:20
  of
• 5:21
  SSRIs
• 5:22
  is
• 5:23
  we
• 5:23
  have
• 5:23
  to
• 5:23
  remember
• 5:24
  it's
• 5:24
  not
• 5:24
  a
• 5:24
  one
• 5:24
  size
• 5:25
  fits
• 5:25
  all
• 5:25
  thing.
• 5:26
  You
• 5:26
  can't
• 5:26
  look
• 5:26
  a
• 5:27
  patient
• 5:27
  in
• 5:27
  the
• 5:27
  eye
• 5:27
  and
• 5:27
  say,
• 5:28
  I'm
• 5:28
  going
• 5:28
  to
• 5:28
  give
• 5:28
  you
• 5:28
  more
• 5:28
  serotonin
• 5:29
  and
• 5:29
  therefore
• 5:30
  you're
• 5:30
  going
• 5:30
  to
• 5:30
  feel
• 5:30
  better.
• 5:31
  That
• 5:31
  is
• 5:31
  a
• 5:31
  very
• 5:32
  unsophisticated
• 5:33
  way
• 5:34
  explaining
• 5:35
  a
• 5:35
  problem
• 5:36
  and
• 5:36
  a
• 5:36
  solution.
• 5:37
  It's
• 5:37
  not
• 5:38
  really
• 5:38
  how
• 5:38
  this
• 5:38
  thing
• 5:39
  works.
• 5:39
  There's
• 5:39
  a
• 5:39
  lot
• 5:39
  of
• 5:40
  nuance
• 5:40
  to
• 5:40
  it.
• 5:41
  You
• 5:41
  know,
• 5:41
  nobody
• 5:42
  expects
• 5:42
  you
• 5:42
  to
• 5:42
  whip
• 5:43
  out
• 5:43
  Stahl's
• 5:44
  textbook
• 5:44
  and
• 5:44
  go
• 5:45
  over
• 5:45
  the
• 5:45
  nitty
• 5:45
  gritty
• 5:46
  neurotransmitters
• 5:47
  picture
• 5:47
  by
• 5:47
  picture
• 5:48
  with
• 5:48
  your
• 5:48
  patients.
• 5:49
  They're
• 5:49
  not
• 5:49
  going
• 5:49
  to
• 5:49
  ask
• 5:49
  you
• 5:50
  that.
• 5:50
  But
• 5:51
  again,
• 5:51
  having
• 5:51
  a
• 5:52
  finer
• 5:52
  appreciation,
• 5:53
  I
• 5:53
  think
• 5:53
  is
• 5:53
  a
• 5:53
  very
• 5:53
  good
• 5:54
  thing.
• 5:55
  Now,
• 5:56
  there
• 5:57
  are
• 5:57
  various
• 5:58
  receptors
• 5:58
  that
• 5:59
  interest
• 5:59
  us
• 5:59
  when
• 6:00
  we
• 6:00
  want
• 6:00
  to
• 6:00
  augment
• 6:02
  with
• 6:03
  second
• 6:03
  generation
• 6:04
  antipsychotics.
• 6:05
  For
• 6:05
  me,
• 6:05
  the
• 6:06
  way
• 6:06
  to
• 6:06
  explain
• 6:06
  this
• 6:07
  or
• 6:07
  think
• 6:07
  about
• 6:07
  it
• 6:07
  most
• 6:08
  constructively
• 6:09
  is
• 6:09
  you
• 6:09
  take
• 6:09
  it
• 6:10
  receptor
• 6:10
  by
• 6:10
  receptor
• 6:11
  and
• 6:12
  start
• 6:12
  with
• 6:12
  what
• 6:13
  serotonin
• 6:13
  does
• 6:14
  in
• 6:14
  general.
• 6:14
  So
• 6:15
  let's
• 6:15
  say
• 6:15
  you
• 6:16
  start
• 6:16
  Lexapro
• 6:17
  and
• 6:17
  your
• 6:17
  patient,
• 6:19
  in
• 6:19
  this
• 6:19
  case,
• 6:19
  our
• 6:19
  mock
• 6:20
  patient,
• 6:21
  will
• 6:21
  be
• 6:21
  Matt.
• 6:22
  Matt
• 6:22
  is
• 6:22
  our
• 6:22
  mock
• 6:23
  patient.
• 6:23
  And
• 6:23
  he
• 6:23
  came
• 6:24
  to
• 6:24
  you
• 6:24
  feeling
• 6:25
  a
• 6:25
  lot
• 6:25
  of
• 6:25
  anxiety,
• 6:26
  a
• 6:27
  lot
• 6:27
  of
• 6:27
  rumination,
• 6:28
  a
• 6:28
  lot
• 6:28
  of
• 6:29
  overthinking,
• 6:30
  and
• 6:30
  he
• 6:31
  really
• 6:31
  needs
• 6:31
  some
• 6:31
  help.
• 6:31
  He
• 6:32
  can't
• 6:32
  sleep
• 6:32
  either,
• 6:32
  and
• 6:32
  he's
• 6:33
  pretty
• 6:33
  scrawny
• 6:33
  and
• 6:34
  he's
• 6:34
  not
• 6:34
  eating.
• 6:34
  So
• 6:35
  you
• 6:35
  got,
• 6:35
  you
• 6:35
  have
• 6:35
  a
• 6:35
  guy
• 6:35
  who
• 6:36
  can't
• 6:36
  eat,
• 6:36
  he
• 6:36
  can't
• 6:36
  sleep,
• 6:37
  and
• 6:37
  he's
• 6:37
  just
• 6:38
  super
• 6:39
  ruminative
• 6:40
  at
• 6:40
  night.
• 6:40
  He's
• 6:40
  anxious.
• 6:41
  He
• 6:41
  wants
• 6:41
  you
• 6:41
  to
• 6:42
  help
• 6:42
  him
• 6:43
  with
• 6:43
  his
• 6:43
  anxiety,
• 6:44
  especially
• 6:44
  at
• 6:45
  night.
• 6:45
  And
• 6:45
  you're
• 6:45
  like,
• 6:46
  well,
• 6:46
  do
• 6:46
  I
• 6:46
  have
• 6:46
  him
• 6:46
  at
• 6:46
  Lexapro?
• 6:47
  Do
• 6:47
  I
• 6:47
  optimize
• 6:48
  the
• 6:48
  Lexapro?
• 6:49
  I
• 6:49
  mean,
• 6:49
  you
• 6:49
  could
• 6:49
  increase
• 6:50
  the
• 6:50
  Lexapro
• 6:51
  maybe,
• 6:51
  right?
• 6:52
  But
• 6:53
  you
• 6:53
  also
• 6:54
  could
• 6:54
  look
• 6:55
  at
• 6:55
  the
• 6:55
  evidence
• 6:55
  and
• 6:56
  say,
• 6:56
  well,
• 6:56
  how
• 6:56
  can
• 6:56
  we
• 6:57
  finally
• 6:57
  target
• 6:57
  these
• 6:58
  symptoms?
• 6:59
  And
• 6:59
  if
• 6:59
  he's
• 6:59
  anxious
• 7:00
  and
• 7:00
  he's
• 7:00
  ruminating
• 7:01
  and
• 7:02
  he's
• 7:02
  not
• 7:02
  sleeping,
• 7:03
  is
• 7:03
  there
• 7:03
  an
• 7:03
  SGA
• 7:05
  that
• 7:05
  might
• 7:05
  fit
• 7:05
  the
• 7:06
  bill?
• 7:06
  Precisely.
• 7:07
  For
• 7:07
  someone
• 7:07
  who
• 7:07
  isn't
• 7:08
  sleeping,
• 7:08
  isn't
• 7:08
  eating,
• 7:09
  and
• 7:09
  is
• 7:09
  ruminating
• 7:09
  too
• 7:10
  much?
• 7:10
  Well,
• 7:10
  turns
• 7:10
  out
• 7:11
  there
• 7:11
  is
• 7:11
  that
• 7:12
  SGA
• 7:12
  that
• 7:13
  we
• 7:13
  can
• 7:13
  look
• 7:13
  at
• 7:14
  in
• 7:14
  just
• 7:14
  a
• 7:14
  moment.
• 7:15
  But
• 7:15
  when
• 7:15
  we
• 7:15
  talk
• 7:16
  about
• 7:17
  Lexapro.
• 7:17
  So
• 7:18
  we
• 7:18
  give
• 7:19
  Matt
• 7:19
  Lexapro
• 7:21
  and
• 7:22
  what
• 7:22
  we
• 7:22
  find
• 7:22
  is
• 7:23
  that
• 7:23
  Lexapro
• 7:24
  will
• 7:24
  activate
• 7:25
  the
• 7:25
  5ht2a
• 7:27
  receptor.
• 7:28
  Now,
• 7:28
  this
• 7:28
  is
• 7:28
  a
• 7:28
  very
• 7:29
  important
• 7:29
  receptor
• 7:30
  as
• 7:30
  it
• 7:30
  relates
• 7:31
  to
• 7:32
  SGA
• 7:32
  augmentation,
• 7:33
  because
• 7:33
  when
• 7:34
  serotonin
• 7:34
  binds
• 7:35
  here,
• 7:35
  especially
• 7:35
  in
• 7:36
  the
• 7:36
  cortex,
• 7:36
  it
• 7:36
  actually
• 7:37
  stimulates
• 7:37
  glutamate
• 7:38
  neurons.
• 7:39
  That's
• 7:39
  very
• 7:40
  important
• 7:40
  because
• 7:40
  that
• 7:40
  extra
• 7:41
  glutamate
• 7:42
  can
• 7:42
  lead
• 7:42
  to
• 7:42
  hyperexcitability,
• 7:44
  racing
• 7:44
  thoughts,
• 7:44
  rumination,
• 7:45
  anxiety,
• 7:46
  and
• 7:46
  poor
• 7:47
  sleep.
• 7:48
  And
• 7:48
  it's
• 7:48
  an
• 7:48
  opportunity
• 7:49
  as
• 7:49
  well,
• 7:50
  because
• 7:50
  a
• 7:51
  lot
• 7:51
  of
• 7:51
  these
• 7:51
  SGAs
• 7:53
  will
• 7:53
  antagonize
• 7:54
  the
• 7:54
  5ht2a
• 7:55
  receptor.
• 7:56
  And
• 7:56
  if
• 7:56
  we
• 7:57
  antagonize
• 7:57
  that
• 7:57
  receptor,
• 7:58
  we
• 7:58
  actually
• 7:59
  do
• 7:59
  the
• 7:59
  opposite,
• 8:00
  where
• 8:00
  we
• 8:01
  regulate
• 8:02
  glutamate
• 8:03
  neurons
• 8:03
  so
• 8:04
  that
• 8:04
  they
• 8:04
  are
• 8:04
  not
• 8:04
  hyperexcitable.
• 8:05
  So
• 8:05
  those
• 8:06
  racing
• 8:06
  thoughts
• 8:06
  can
• 8:06
  actually
• 8:07
  calm
• 8:07
  down.
• 8:08
  So
• 8:08
  you
• 8:08
  can
• 8:08
  ruminate
• 8:09
  less,
• 8:09
  you
• 8:09
  can
• 8:09
  be
• 8:09
  less
• 8:10
  anxious,
• 8:10
  and
• 8:10
  that
• 8:10
  might
• 8:10
  be
• 8:11
  able
• 8:11
  to
• 8:11
  promote
• 8:11
  sleep
• 8:12
  indirectly,
• 8:13
  of
• 8:13
  course,
• 8:13
  because
• 8:13
  if
• 8:13
  you're
• 8:13
  not
• 8:14
  as
• 8:14
  anxious
• 8:14
  and
• 8:14
  you're
• 8:14
  not
• 8:14
  ruminating
• 8:15
  as
• 8:15
  much,
• 8:15
  you
• 8:15
  might
• 8:16
  be
• 8:16
  able
• 8:16
  to
• 8:16
  sleep
• 8:16
  more.
• 8:16
  So
• 8:17
  we
• 8:17
  have
• 8:17
  to
• 8:17
  find
• 8:17
  something
• 8:18
  that
• 8:18
  antagonizes
• 8:19
  5ht
• 8:19
  2a.
• 8:20
  We
• 8:20
  have
• 8:21
  pretty
• 8:21
  good
• 8:21
  candidates
• 8:22
  for
• 8:22
  that.
• 8:22
  No
• 8:22
  need
• 8:23
  to
• 8:23
  memorize
• 8:23
  what
• 8:23
  those
• 8:23
  candidates
• 8:24
  are
• 8:24
  right
• 8:24
  now.
• 8:25
  I
• 8:25
  will
• 8:25
  share
• 8:25
  those
• 8:26
  with
• 8:26
  you
• 8:26
  later.
• 8:27
  Suffice
• 8:27
  it
• 8:27
  to
• 8:27
  say,
• 8:28
  we
• 8:28
  have
• 8:29
  pretty
• 8:29
  good
• 8:29
  candidates
• 8:30
  for
• 8:30
  that.
• 8:30
  One
• 8:31
  little
• 8:31
  sneak
• 8:31
  peek
• 8:32
  is
• 8:32
  quetiapine
• 8:33
  or
• 8:33
  seroquel
• 8:34
  is
• 8:34
  a
• 8:34
  good
• 8:34
  one
• 8:35
  for
• 8:35
  that
• 8:35
  particular
• 8:36
  receptor.
• 8:37
  Now,
• 8:38
  there's
• 8:38
  other
• 8:38
  receptors
• 8:39
  that
• 8:39
  we
• 8:39
  ought
• 8:40
  to
• 8:40
  keep
• 8:40
  in
• 8:40
  mind
• 8:40
  when
• 8:41
  our
• 8:41
  patient
• 8:41
  has
• 8:41
  an
• 8:41
  incomplete
• 8:43
  response
• 8:44
  and
• 8:44
  they're
• 8:44
  not
• 8:44
  in
• 8:44
  remission
• 8:45
  yet
• 8:45
  with
• 8:46
  respect
• 8:46
  to
• 8:46
  their
• 8:46
  depression.
• 8:47
  You
• 8:48
  can
• 8:48
  look
• 8:48
  at
• 8:49
  folks
• 8:49
  who
• 8:50
  have
• 8:50
  anxiety.
• 8:51
  They're
• 8:52
  still
• 8:52
  anxious.
• 8:52
  They're
• 8:52
  depressed,
• 8:53
  but
• 8:53
  they
• 8:54
  have
• 8:54
  an
• 8:54
  anxious
• 8:54
  depression.
• 8:55
  Right?
• 8:55
  So
• 8:56
  you
• 8:56
  might
• 8:56
  want
• 8:56
  to
• 8:56
  find
• 8:56
  a
• 8:57
  SGA
• 8:57
  that
• 8:58
  targets
• 8:58
  the
• 8:58
  autoreceptor
• 8:59
  of
• 8:59
  5ht1a.
• 9:01
  This
• 9:01
  is
• 9:02
  a
• 9:02
  very
• 9:02
  complicated
• 9:02
  receptor,
• 9:03
  but
• 9:03
  Basically
• 9:04
  think
• 9:04
  of
• 9:04
  5ht1a
• 9:05
  as
• 9:06
  serotonin's
• 9:06
  brake
• 9:06
  pedal.
• 9:07
  When
• 9:07
  serotonin
• 9:08
  binds
• 9:08
  there,
• 9:08
  it
• 9:09
  tells
• 9:09
  the
• 9:09
  neurons
• 9:10
  stop
• 9:10
  releasing
• 9:10
  more
• 9:11
  serotonin.
• 9:12
  Right.
• 9:12
  And
• 9:13
  that's
• 9:13
  why
• 9:13
  some
• 9:13
  of
• 9:13
  your
• 9:14
  patients
• 9:14
  can
• 9:14
  get
• 9:14
  pretty
• 9:15
  anxious,
• 9:15
  because
• 9:15
  when
• 9:15
  you
• 9:15
  start
• 9:16
  something
• 9:16
  like
• 9:16
  Lexapro,
• 9:17
  and
• 9:17
  Matt
• 9:17
  started
• 9:18
  Lexapro,
• 9:19
  and
• 9:19
  he
• 9:19
  actually
• 9:19
  it
• 9:20
  caused
• 9:20
  that
• 9:20
  autoreceptor
• 9:21
  to
• 9:21
  stop
• 9:22
  the
• 9:22
  release
• 9:22
  of
• 9:22
  serotonin.
• 9:23
  When
• 9:23
  you
• 9:23
  stop
• 9:24
  the
• 9:24
  release
• 9:24
  of
• 9:24
  serotonin,
• 9:25
  you
• 9:25
  might
• 9:25
  feel
• 9:25
  more
• 9:26
  anxious
• 9:26
  for
• 9:26
  a
• 9:26
  little
• 9:26
  while
• 9:27
  until
• 9:28
  what
• 9:28
  happens?
• 9:29
  Brain
• 9:29
  starts
• 9:30
  to
• 9:31
  re
• 9:31
  regulate
• 9:32
  and
• 9:32
  actually
• 9:33
  create
• 9:33
  more
• 9:33
  serotonin
• 9:35
  after
• 9:35
  a
• 9:35
  while
• 9:36
  because
• 9:36
  you've
• 9:37
  pushed
• 9:37
  the
• 9:37
  brake.
• 9:37
  And
• 9:38
  then
• 9:38
  it
• 9:38
  gets
• 9:38
  desensitized.
• 9:39
  Eventually
• 9:40
  it
• 9:40
  will
• 9:40
  start
• 9:41
  releasing
• 9:41
  more
• 9:42
  serotonin
• 9:43
  because
• 9:43
  you've
• 9:43
  deprived
• 9:44
  it
• 9:44
  of
• 9:44
  serotonin
• 9:45
  for
• 9:45
  so
• 9:45
  long.
• 9:46
  And
• 9:46
  that's
• 9:47
  our
• 9:47
  homeostatic
• 9:48
  way
• 9:48
  of
• 9:48
  doing
• 9:48
  things.
• 9:49
  When
• 9:49
  you
• 9:50
  first
• 9:50
  start
• 9:51
  an
• 9:51
  SSRI,
• 9:52
  you're
• 9:52
  hitting
• 9:52
  that
• 9:52
  autoreceptor,
• 9:53
  that
• 9:53
  5ht1a
• 9:54
  autoreceptor.
• 9:55
  It
• 9:55
  pumps
• 9:55
  the
• 9:55
  brakes
• 9:56
  on
• 9:56
  serotonin,
• 9:57
  and
• 9:57
  you
• 9:57
  can
• 9:57
  potentially
• 9:57
  get
• 9:58
  more
• 9:58
  anxious.
• 9:58
  That
• 9:58
  can
• 9:58
  be
• 9:59
  very
• 9:59
  destabilizing
• 10:00
  for
• 10:00
  people.
• 10:01
  So
• 10:01
  when
• 10:01
  you
• 10:01
  look
• 10:01
  at
• 10:02
  someone
• 10:02
  who's
• 10:02
  still
• 10:02
  anxious
• 10:03
  and
• 10:03
  you
• 10:03
  started
• 10:03
  Lexapro
• 10:04
  and
• 10:05
  they
• 10:05
  have
• 10:05
  anxious
• 10:05
  depression,
• 10:06
  you
• 10:06
  can
• 10:06
  look
• 10:06
  at
• 10:07
  a
• 10:07
  partial
• 10:07
  agonist
• 10:08
  at
• 10:08
  5ht
• 10:09
  1a,
• 10:10
  like
• 10:11
  Abilify
• 10:12
  or
• 10:12
  Brexpriprazole,
• 10:13
  can
• 10:14
  put
• 10:14
  a
• 10:14
  little
• 10:15
  bit
• 10:15
  of
• 10:15
  the
• 10:15
  gas
• 10:16
  pedal
• 10:16
  on
• 10:16
  5ht1a.
• 10:17
  Instead
• 10:18
  of
• 10:18
  fully
• 10:18
  slamming
• 10:19
  the
• 10:19
  brakes
• 10:19
  on
• 10:19
  serotonin,
• 10:20
  they're
• 10:20
  just
• 10:20
  partially
• 10:21
  doing
• 10:21
  it
• 10:21
  so
• 10:21
  that
• 10:21
  there's
• 10:22
  a
• 10:22
  little
• 10:22
  bit
• 10:22
  of
• 10:22
  serotonin
• 10:23
  still
• 10:23
  flowing
• 10:24
  around.
• 10:25
  Partial
• 10:25
  agonists
• 10:25
  are
• 10:26
  like
• 10:26
  a
• 10:26
  dimmer
• 10:26
  switch.
• 10:26
  They
• 10:26
  don't
• 10:27
  go
• 10:27
  all
• 10:28
  or
• 10:28
  nothing.
• 10:28
  There's
• 10:28
  a
• 10:28
  bit
• 10:29
  of
• 10:29
  modulation
• 10:29
  there,
• 10:30
  and
• 10:30
  that
• 10:30
  can
• 10:30
  actually
• 10:30
  be
• 10:31
  pretty
• 10:32
  darn
• 10:33
  helpful.
• 10:33
  Also,
• 10:34
  think
• 10:34
  about
• 10:35
  the
• 10:36
  fact
• 10:36
  that
• 10:36
  in
• 10:36
  addition
• 10:36
  to
• 10:37
  5ht1a
• 10:38
  autoreceptors,
• 10:38
  you
• 10:38
  have
• 10:38
  postsynaptic
• 10:39
  5ht1a
• 10:40
  receptors.
• 10:42
  And
• 10:42
  these
• 10:42
  receptors
• 10:43
  sit
• 10:43
  on
• 10:43
  target
• 10:44
  neurons,
• 10:44
  often
• 10:45
  glutamate
• 10:45
  neurons.
• 10:46
  So
• 10:46
  when
• 10:47
  you
• 10:47
  activate
• 10:47
  them,
• 10:48
  it
• 10:48
  actually
• 10:48
  hyperpolarizes
• 10:49
  them
• 10:49
  and
• 10:49
  quiets
• 10:50
  them
• 10:50
  down.
• 10:50
  Again,
• 10:50
  these
• 10:51
  are
• 10:51
  the
• 10:51
  postsynaptic,
• 10:52
  not
• 10:52
  the
• 10:52
  autoreceptor.
• 10:53
  It
• 10:53
  gets
• 10:53
  very
• 10:53
  confusing.
• 10:54
  You
• 10:54
  have
• 10:54
  5ht
• 10:55
  5h
• 10:56
  T1a
• 10:56
  autoreceptors
• 10:57
  and
• 10:58
  5ht
• 10:58
  1a
• 10:59
  postsynaptic
• 11:00
  receptors.
• 11:01
  And
• 11:01
  remember,
• 11:01
  these
• 11:02
  receptors
• 11:02
  are
• 11:03
  in
• 11:03
  various
• 11:03
  parts
• 11:04
  of
• 11:04
  the
• 11:04
  brain.
• 11:04
  So
• 11:05
  hopefully
• 11:05
  you're
• 11:05
  gaining
• 11:06
  an
• 11:06
  appreciation
• 11:06
  for
• 11:06
  this
• 11:07
  and
• 11:07
  the
• 11:07
  complexity
• 11:07
  of
• 11:08
  this.
• 11:08
  If
• 11:08
  it
• 11:08
  sounds
• 11:09
  confusing,
• 11:09
  it
• 11:10
  should
• 11:10
  be.
• 11:11
  Embrace
• 11:11
  that,
• 11:12
  because
• 11:12
  it
• 11:12
  gives
• 11:12
  you
• 11:13
  a
• 11:13
  depth
• 11:13
  of
• 11:13
  understanding
• 11:14
  and
• 11:14
  appreciation
• 11:15
  for
• 11:15
  this.
• 11:15
  Because
• 11:15
  when
• 11:15
  you
• 11:15
  start
• 11:16
  a
• 11:16
  medication,
• 11:16
  it's
• 11:17
  not
• 11:17
  as
• 11:17
  simple
• 11:17
  as
• 11:18
  one
• 11:18
  thing
• 11:19
  that
• 11:19
  happens.
• 11:19
  You
• 11:20
  have
• 11:20
  various
• 11:20
  parts
• 11:20
  of
• 11:21
  the
• 11:21
  brain
• 11:21
  that
• 11:22
  have
• 11:22
  varieties
• 11:22
  of
• 11:23
  receptors
• 11:24
  associated
• 11:25
  with
• 11:25
  those
• 11:25
  parts
• 11:25
  of
• 11:25
  the
• 11:25
  brain
• 11:26
  and
• 11:26
  circuitry.
• 11:27
  And
• 11:27
  depending
• 11:27
  on
• 11:28
  the
• 11:28
  agent
• 11:29
  you
• 11:29
  use,
• 11:29
  it
• 11:29
  acts
• 11:30
  on
• 11:30
  those
• 11:30
  receptors
• 11:30
  differently
• 11:31
  to
• 11:32
  produce
• 11:32
  different
• 11:32
  outcomes.
• 11:33
  We're
• 11:33
  talking
• 11:34
  about
• 11:34
  the
• 11:34
  postsynaptic
• 11:35
  5ht1a
• 11:36
  receptors,
• 11:37
  often
• 11:37
  in
• 11:37
  the
• 11:37
  cortex,
• 11:38
  the
• 11:38
  hippocampus,
• 11:39
  the
• 11:39
  amygdala,
• 11:39
  the
• 11:39
  fight
• 11:40
  or
• 11:40
  flight,
• 11:40
  the
• 11:40
  memory,
• 11:41
  the
• 11:41
  thinking,
• 11:41
  and
• 11:41
  higher
• 11:42
  cognitions.
• 11:42
  When
• 11:43
  you
• 11:43
  activate
• 11:43
  these
• 11:44
  five
• 11:44
  HT1A
• 11:45
  receptors
• 11:45
  with
• 11:46
  your
• 11:46
  SGAs,
• 11:47
  you
• 11:48
  hyperpolarize
• 11:49
  them
• 11:49
  and
• 11:49
  quiet
• 11:49
  them
• 11:49
  down.
• 11:50
  The
• 11:50
  net
• 11:50
  effect
• 11:50
  is
• 11:51
  less
• 11:51
  excitatory
• 11:51
  chatter,
• 11:52
  less
• 11:53
  amygdala
• 11:53
  overdrive,
• 11:54
  and
• 11:54
  you
• 11:55
  get
• 11:55
  some
• 11:55
  anxiolysis
• 11:56
  and
• 11:56
  mood
• 11:56
  stability.
• 11:57
  You
• 11:57
  can
• 11:57
  actually
• 11:58
  calm
• 11:58
  things
• 11:58
  down.
• 11:59
  And
• 11:59
  this
• 11:59
  is
• 11:59
  where
• 11:59
  it
• 12:00
  gets
• 12:00
  a
• 12:00
  little
• 12:00
  confusing.
• 12:01
  But
• 12:01
  once
• 12:01
  you
• 12:01
  calm
• 12:02
  things
• 12:02
  down
• 12:03
  with
• 12:03
  that
• 12:03
  amygdala
• 12:04
  overdrive
• 12:05
  and
• 12:05
  that
• 12:05
  anxiety,
• 12:06
  what
• 12:07
  actually
• 12:07
  happens
• 12:07
  as
• 12:08
  that
• 12:08
  glutamate
• 12:09
  calms
• 12:09
  down?
• 12:09
  Remember,
• 12:10
  these
• 12:10
  receptors
• 12:11
  sit
• 12:11
  on
• 12:11
  target
• 12:11
  neurons.
• 12:12
  The
• 12:12
  five
• 12:12
  HT1A
• 12:13
  receptors
• 12:13
  sit
• 12:13
  on
• 12:14
  target
• 12:14
  neurons,
• 12:14
  often
• 12:15
  glutamate
• 12:15
  neurons.
• 13:10
  When
• 13:11
  you
• 13:11
  choose
• 13:11
  an
• 13:12
  SGA
• 13:13
  that
• 13:13
  targets
• 13:14
  5ht1a
• 13:15
  post
• 13:15
  synaptic
• 13:16
  receptors,
• 13:17
  often
• 13:18
  on
• 13:18
  glutamate
• 13:18
  neurons,
• 13:19
  you
• 13:19
  get
• 13:20
  less
• 13:20
  of
• 13:20
  an
• 13:21
  excitatory
• 13:21
  chatter.
• 13:22
  Glutamate
• 13:23
  in
• 13:23
  excess
• 13:23
  can
• 13:24
  be
• 13:24
  very
• 13:24
  excitatory,
• 13:26
  so
• 13:26
  you
• 13:26
  get
• 13:26
  less
• 13:26
  of
• 13:26
  excitatory
• 13:27
  chatter.
• 13:28
  The
• 13:28
  amygdala
• 13:29
  is
• 13:29
  less
• 13:29
  in
• 13:29
  overdrive
• 13:30
  and
• 13:30
  you
• 13:30
  get
• 13:30
  anxiolysis
• 13:31
  and
• 13:31
  mood
• 13:31
  stability
• 13:32
  because
• 13:32
  you're
• 13:32
  less
• 13:32
  anxious.
• 13:33
  The
• 13:33
  dopamine
• 13:34
  can
• 13:34
  shine
• 13:34
  a
• 13:35
  little
• 13:35
  more
• 13:35
  because
• 13:36
  that
• 13:36
  signal
• 13:36
  of
• 13:36
  dopamine
• 13:37
  tends
• 13:37
  to
• 13:37
  be
• 13:37
  drowned
• 13:38
  out
• 13:38
  when
• 13:38
  there's
• 13:38
  too
• 13:39
  much
• 13:39
  anxiety,
• 13:40
  when
• 13:40
  there's
• 13:40
  too
• 13:40
  much
• 13:40
  excess
• 13:41
  glutamate
• 13:42
  activity.
• 13:43
  This
• 13:43
  is
• 13:43
  another
• 13:43
  way
• 13:44
  for
• 13:44
  you
• 13:44
  to
• 13:44
  let
• 13:44
  dopamine
• 13:45
  shine,
• 13:45
  let
• 13:45
  motivation
• 13:46
  and
• 13:46
  cognition
• 13:47
  shine,
• 13:47
  because
• 13:48
  you're
• 13:48
  dampening
• 13:49
  the
• 13:49
  excessive
• 13:50
  anxiety
• 13:51
  response
• 13:52
  associated
• 13:52
  with
• 13:53
  with
• 13:53
  glutamate,
• 13:53
  the
• 13:54
  rumination,
• 13:54
  the
• 13:54
  noise.
• 13:55
  Now,
• 13:55
  we
• 13:56
  have
• 13:56
  other
• 13:56
  receptors
• 13:57
  that
• 13:57
  are
• 13:57
  very,
• 13:58
  very
• 13:58
  interesting.
• 13:59
  We
• 13:59
  talked
• 14:00
  a
• 14:00
  little
• 14:00
  bit
• 14:01
  about
• 14:01
  five
• 14:02
  HT1A
• 14:03
  autoreceptors.
• 14:04
  We
• 14:05
  talked
• 14:05
  about
• 14:05
  the
• 14:05
  postsynaptic
• 14:06
  receptors.
• 14:07
  We
• 14:07
  really
• 14:08
  want
• 14:08
  again
• 14:08
  to
• 14:09
  antagonize
• 14:10
  the
• 14:10
  5ht2a
• 14:11
  receptor
• 14:12
  here,
• 14:12
  like
• 14:12
  I
• 14:12
  said,
• 14:13
  because
• 14:13
  when
• 14:13
  serotonin
• 14:14
  binds
• 14:14
  here,
• 14:14
  especially
• 14:15
  in
• 14:15
  the
• 14:15
  cortex,
• 14:15
  it
• 14:16
  stimulates
• 14:16
  glutamate
• 14:18
  neurons.
• 14:19
  So
• 14:19
  what's
• 14:19
  happening
• 14:19
  with
• 14:19
  Matt
• 14:20
  is
• 14:20
  Lexapro
• 14:21
  stimulating
• 14:21
  these
• 14:21
  glutamate
• 14:22
  neurons.
• 14:22
  There's
• 14:22
  a
• 14:22
  lot
• 14:22
  of
• 14:22
  excess
• 14:23
  noise,
• 14:23
  rumination,
• 14:24
  chatter,
• 14:24
  that's
• 14:25
  driving
• 14:25
  him
• 14:25
  nuts
• 14:26
  and
• 14:26
  keeping
• 14:26
  him
• 14:26
  awake
• 14:26
  at
• 14:27
  night.
• 14:27
  And
• 14:28
  so
• 14:28
  if
• 14:28
  we
• 14:28
  antagonize
• 14:29
  that
• 14:29
  a
• 14:29
  little
• 14:29
  bit
• 14:30
  with
• 14:30
  something
• 14:30
  like
• 14:30
  Seroquel,
• 14:31
  we're
• 14:31
  going
• 14:32
  to
• 14:32
  actually
• 14:32
  make
• 14:32
  the
• 14:33
  rumination
• 14:33
  and
• 14:33
  chatter
• 14:34
  go
• 14:35
  down.
• 14:36
  Now,
• 14:36
  there's
• 14:36
  other
• 14:37
  methods
• 14:37
  to
• 14:38
  augment
• 14:39
  with
• 14:39
  SGAs
• 14:40
  and
• 14:40
  other
• 14:40
  receptor
• 14:41
  targets,
• 14:41
  one
• 14:42
  of
• 14:42
  them
• 14:42
  being
• 14:42
  5HT2C.
• 14:44
  The
• 14:44
  5
• 14:45
  HT2C
• 14:45
  is
• 14:45
  the
• 14:45
  weight
• 14:46
  gainer.
• 14:46
  When
• 14:46
  you
• 14:47
  antagonize
• 14:47
  5
• 14:48
  HT2C,
• 14:49
  it
• 14:50
  leads
• 14:50
  to
• 14:50
  weight
• 14:50
  gain
• 14:51
  and
• 14:51
  SGAs
• 14:52
  that
• 14:53
  antagonize
• 14:53
  it
• 14:54
  very
• 14:54
  aggressively,
• 14:55
  like
• 14:55
  Zyprexa,
• 14:57
  are
• 14:57
  known
• 14:58
  to
• 14:58
  cause
• 14:58
  weight
• 14:59
  gain,
• 14:59
  and
• 15:00
  that
• 15:00
  is
• 15:00
  problematic.
• 15:01
  There's
• 15:01
  always
• 15:02
  trade
• 15:02
  offs
• 15:02
  to
• 15:03
  this
• 15:03
  because,
• 15:04
  you
• 15:04
  know,
• 15:05
  you
• 15:05
  modulate
• 15:06
  the
• 15:06
  depression
• 15:06
  or
• 15:07
  you
• 15:07
  augment
• 15:07
  in
• 15:07
  major
• 15:08
  depression,
• 15:08
  but
• 15:08
  you're
• 15:08
  causing
• 15:09
  weight
• 15:09
  gain.
• 15:10
  Now,
• 15:10
  what
• 15:10
  is
• 15:10
  5ht2c
• 15:12
  doing
• 15:12
  exactly?
• 15:12
  Again,
• 15:13
  we
• 15:13
  talked
• 15:13
  about
• 15:13
  the
• 15:13
  weight
• 15:14
  gain,
• 15:14
  but
• 15:15
  very
• 15:15
  interestingly,
• 15:16
  my
• 15:16
  friends,
• 15:17
  when
• 15:17
  we
• 15:18
  use
• 15:18
  a
• 15:18
  5ht
• 15:19
  2c
• 15:20
  antagonist,
• 15:22
  we
• 15:22
  actually
• 15:23
  unleash
• 15:23
  dopamine
• 15:24
  and
• 15:24
  norepinephrine
• 15:25
  in
• 15:25
  the
• 15:25
  prefrontal
• 15:26
  cortex,
• 15:26
  which
• 15:26
  allows
• 15:27
  patients
• 15:27
  to
• 15:27
  feel
• 15:28
  less
• 15:28
  foggy,
• 15:28
  less
• 15:28
  restless,
• 15:29
  and
• 15:29
  we
• 15:29
  let
• 15:30
  them
• 15:30
  feel
• 15:30
  more
• 15:31
  motivated.
• 15:32
  Very,
• 15:32
  very
• 15:32
  neat.
• 15:33
  Because
• 15:33
  when
• 15:34
  we
• 15:34
  activate
• 15:34
  5ht
• 15:35
  2c,
• 15:35
  we
• 15:35
  actually
• 15:36
  clamp
• 15:36
  down
• 15:36
  on
• 15:37
  dopamine
• 15:37
  and
• 15:37
  norepinephrine
• 15:38
  in
• 15:38
  the
• 15:38
  prefrontal
• 15:39
  cortex.
• 15:40
  Lexapro
• 15:40
  dose
• 15:41
  it's
• 15:41
  activating
• 15:41
  5ht
• 15:42
  2c.
• 15:42
  So
• 15:42
  it's
• 15:43
  clamping
• 15:43
  down
• 15:43
  on
• 15:44
  dopamine
• 15:44
  and
• 15:44
  norepinephrine.
• 15:45
  Well,
• 15:45
  lo
• 15:45
  and
• 15:46
  behold,
• 15:46
  that's
• 15:46
  going
• 15:46
  to
• 15:46
  make
• 15:46
  him
• 15:47
  feeling
• 15:47
  foggy,
• 15:47
  restless
• 15:48
  and
• 15:48
  unmotivated.
• 15:49
  So
• 15:49
  one
• 15:50
  target
• 15:50
  here
• 15:51
  is
• 15:51
  to
• 15:51
  find
• 15:52
  an
• 15:52
  SGA
• 15:52
  that
• 15:53
  antagonizes
• 15:53
  5ht
• 15:54
  2c.
• 15:55
  Now,
• 15:55
  you
• 15:55
  have
• 15:55
  to
• 15:55
  do
• 15:56
  this
• 15:56
  carefully,
• 15:56
  though,
• 15:56
  and
• 15:57
  this
• 15:57
  is
• 15:57
  where
• 15:57
  the
• 15:57
  side
• 15:57
  effects
• 15:58
  come
• 15:58
  in,
• 15:58
  because
• 15:59
  5ht
• 16:00
  2c
• 16:01
  will
• 16:01
  cause
• 16:01
  weight
• 16:02
  gain.
• 16:02
  Now,
• 16:02
  there's
• 16:02
  another
• 16:03
  podcast
• 16:04
  episode
• 16:04
  about
• 16:05
  this,
• 16:05
  specifically
• 16:06
  using
• 16:06
  a
• 16:06
  really
• 16:06
  elegant
• 16:07
  movie
• 16:07
  theater
• 16:08
  analogy.
• 16:08
  I
• 16:08
  highly
• 16:09
  recommend
• 16:09
  you
• 16:09
  to
• 16:09
  dig
• 16:10
  that
• 16:10
  up
• 16:11
  and
• 16:11
  find
• 16:11
  where
• 16:11
  that
• 16:11
  is.
• 16:12
  It's
• 16:12
  going
• 16:12
  to
• 16:12
  be
• 16:12
  very
• 16:12
  fun
• 16:13
  episode
• 16:13
  for
• 16:13
  you.
• 16:14
  But
• 16:14
  in
• 16:14
  that
• 16:14
  episode,
• 16:15
  we
• 16:15
  liken
• 16:15
  the
• 16:15
  5ht2c
• 16:16
  receptor
• 16:17
  to
• 16:17
  a
• 16:18
  cashier
• 16:18
  or
• 16:19
  a
• 16:19
  clerk
• 16:19
  that's
• 16:20
  manning
• 16:20
  the
• 16:20
  popcorn
• 16:21
  stand
• 16:21
  at
• 16:22
  a
• 16:22
  movie
• 16:22
  theater,
• 16:22
  and
• 16:23
  they're
• 16:23
  selling
• 16:23
  popcorn
• 16:24
  and
• 16:24
  snow
• 16:24
  caps
• 16:25
  and
• 16:25
  Twizzlers
• 16:25
  and
• 16:25
  Reese's
• 16:26
  pieces
• 16:26
  and
• 16:27
  blocking.
• 16:27
  5ht
• 16:28
  2c
• 16:29
  is
• 16:29
  basically
• 16:29
  like
• 16:29
  the
• 16:30
  movie
• 16:31
  owner
• 16:31
  going
• 16:32
  to
• 16:32
  the
• 16:32
  cashiers
• 16:33
  and
• 16:33
  saying,
• 16:33
  why
• 16:33
  don't
• 16:33
  you
• 16:33
  guys
• 16:33
  leave
• 16:34
  and
• 16:34
  go
• 16:34
  take
• 16:34
  a
• 16:34
  break?
• 16:34
  Why
• 16:35
  don't
• 16:35
  you
• 16:35
  just
• 16:35
  leave
• 16:35
  the
• 16:36
  food
• 16:36
  carts
• 16:36
  for
• 16:36
  a
• 16:36
  while
• 16:37
  and
• 16:37
  go
• 16:37
  take
• 16:37
  a
• 16:37
  break?
• 16:38
  In
• 16:38
  other
• 16:38
  words,
• 16:38
  they're
• 16:38
  antagonizing
• 16:40
  the
• 16:40
  five
• 16:40
  HT2C
• 16:41
  clerks.
• 16:42
  They're
• 16:42
  kicking
• 16:43
  them
• 16:43
  out
• 16:43
  of
• 16:43
  their
• 16:43
  job,
• 16:44
  making
• 16:44
  them
• 16:44
  leave.
• 16:45
  They're
• 16:45
  blocking
• 16:45
  them
• 16:45
  from
• 16:46
  doing
• 16:46
  their
• 16:46
  jobs
• 16:46
  and
• 16:46
  go
• 16:47
  take
• 16:47
  a
• 16:47
  break.
• 16:47
  And
• 16:48
  what
• 16:48
  happens
• 16:48
  is
• 16:48
  it's
• 16:48
  a
• 16:48
  free
• 16:49
  for
• 16:49
  all.
• 16:49
  Everybody
• 16:49
  just
• 16:50
  kind
• 16:50
  of
• 16:50
  raids
• 16:50
  the
• 16:50
  candy
• 16:51
  stand
• 16:51
  and
• 16:51
  they
• 16:51
  gain
• 16:51
  tons
• 16:52
  of
• 16:52
  weight.
• 16:52
  The
• 16:52
  5ht2C
• 16:53
  mnemonic.
• 16:54
  The
• 16:54
  C
• 16:54
  is
• 16:54
  for
• 16:55
  candy.
• 16:55
  Candy.
• 16:56
  That
• 16:56
  is
• 16:56
  how
• 16:57
  you
• 16:57
  know
• 16:57
  it
• 16:57
  is
• 16:57
  actually
• 16:58
  going
• 16:58
  to
• 16:58
  cause
• 16:58
  weight
• 16:59
  gain.
• 16:59
  SSRIs
• 17:00
  come
• 17:00
  in,
• 17:01
  they
• 17:01
  activate
• 17:01
  the
• 17:01
  5
• 17:02
  HT2C
• 17:02
  receptor.
• 17:03
  What
• 17:03
  does
• 17:03
  that
• 17:04
  do?
• 17:04
  It
• 17:04
  puts
• 17:05
  a
• 17:05
  brake
• 17:05
  on
• 17:06
  dopamine
• 17:06
  and
• 17:06
  norepinephrine
• 17:07
  in
• 17:07
  the
• 17:07
  prefrontal
• 17:08
  cortex.
• 17:08
  What
• 17:08
  does
• 17:08
  that
• 17:09
  do?
• 17:09
  Patients
• 17:09
  feel
• 17:10
  foggy,
• 17:10
  restless,
• 17:10
  unmotivated.
• 17:11
  We
• 17:12
  don't
• 17:12
  want
• 17:12
  that
• 17:12
  if
• 17:12
  we
• 17:12
  want
• 17:13
  to
• 17:13
  bring
• 17:13
  that
• 17:13
  back
• 17:13
  on
• 17:13
  board.
• 17:14
  You
• 17:14
  want
• 17:14
  to
• 17:14
  find
• 17:14
  something
• 17:14
  that
• 17:15
  antagonizes
• 17:16
  5ht
• 17:16
  2c.
• 17:17
  Well,
• 17:17
  the
• 17:17
  best
• 17:18
  one
• 17:18
  would
• 17:18
  be
• 17:18
  Zyprexa,
• 17:19
  but
• 17:19
  that
• 17:20
  might
• 17:20
  be
• 17:20
  shooting
• 17:20
  squirrels
• 17:21
  with
• 17:21
  rocket
• 17:21
  launchers.
• 17:22
  Because
• 17:22
  Zyprexa
• 17:23
  is
• 17:23
  very
• 17:23
  powerful,
• 17:24
  you
• 17:24
  might
• 17:24
  get
• 17:25
  a
• 17:25
  robust
• 17:25
  improvement
• 17:26
  in
• 17:26
  mood,
• 17:26
  motivation
• 17:27
  and
• 17:27
  drive,
• 17:27
  but
• 17:28
  at
• 17:28
  what
• 17:28
  cost,
• 17:28
  right?
• 17:29
  I've
• 17:29
  had
• 17:29
  patients
• 17:30
  gain
• 17:30
  30
• 17:30
  pounds
• 17:31
  in
• 17:31
  a
• 17:31
  month
• 17:31
  on
• 17:31
  Zyprexa.
• 17:32
  So
• 17:32
  you
• 17:33
  don't
• 17:33
  want
• 17:33
  to
• 17:33
  create
• 17:34
  a
• 17:34
  bit
• 17:34
  more
• 17:34
  of
• 17:35
  diabetes.
• 17:35
  And
• 17:36
  now
• 17:36
  they
• 17:36
  don't
• 17:36
  want
• 17:36
  to
• 17:36
  get
• 17:37
  off
• 17:37
  the
• 17:37
  couch
• 17:37
  because
• 17:37
  they're
• 17:38
  30
• 17:38
  pounds
• 17:38
  heavier.
• 17:38
  So
• 17:39
  there
• 17:39
  are
• 17:39
  trade
• 17:40
  offs
• 17:40
  to
• 17:40
  this,
• 17:40
  right?
• 17:41
  So
• 17:41
  do
• 17:41
  you
• 17:42
  go
• 17:42
  to
• 17:42
  an
• 17:42
  SGA
• 17:42
  that
• 17:43
  has
• 17:43
  5ht
• 17:44
  2c
• 17:45
  blockade,
• 17:45
  but
• 17:45
  a
• 17:45
  little
• 17:46
  less?
• 17:46
  So
• 17:46
  maybe
• 17:47
  Quetiapine.
• 17:47
  That's
• 17:48
  a
• 17:48
  weight
• 17:48
  gainer.
• 17:48
  It
• 17:48
  can
• 17:49
  cause
• 17:49
  weight
• 17:49
  gain.
• 17:50
  Now,
• 17:50
  you
• 17:50
  will
• 17:50
  see
• 17:51
  this
• 17:51
  in
• 17:51
  practice,
• 17:51
  my
• 17:52
  friends,
• 17:52
  that
• 17:52
  even
• 17:52
  though
• 17:52
  your
• 17:53
  textbooks
• 17:53
  say
• 17:54
  they
• 17:54
  cause
• 17:54
  weight
• 17:54
  gain,
• 17:55
  and
• 17:55
  they
• 17:55
  do,
• 17:56
  you
• 17:57
  might
• 17:57
  have
• 17:57
  a
• 17:57
  patient
• 17:57
  or
• 17:58
  two
• 17:58
  that
• 17:58
  for
• 17:59
  whatever
• 17:59
  reason
• 17:59
  can
• 18:00
  be
• 18:00
  out
• 18:00
  on
• 18:00
  Seroquel
• 18:01
  and
• 18:01
  just
• 18:01
  not
• 18:01
  gain
• 18:02
  weight,
• 18:02
  and
• 18:02
  you're
• 18:03
  amazed
• 18:03
  by
• 18:03
  it.
• 18:03
  It's
• 18:03
  like,
• 18:04
  wow,
• 18:04
  this
• 18:04
  is
• 18:04
  supposed
• 18:04
  to
• 18:05
  cause
• 18:05
  weight
• 18:05
  gain.
• 18:05
  And
• 18:05
  it
• 18:06
  does.
• 18:06
  You
• 18:06
  have
• 18:07
  tons
• 18:07
  of
• 18:07
  patients
• 18:07
  who
• 18:07
  gain
• 18:08
  weight
• 18:08
  on
• 18:08
  it,
• 18:08
  and
• 18:08
  then
• 18:08
  all
• 18:08
  of
• 18:09
  a
• 18:09
  sudden
• 18:09
  you
• 18:09
  meet
• 18:09
  a
• 18:09
  patient
• 18:10
  and
• 18:10
  they
• 18:10
  really
• 18:11
  don't
• 18:11
  gain
• 18:11
  weight
• 18:11
  on
• 18:12
  it.
• 18:12
  Now,
• 18:12
  that
• 18:12
  doesn't
• 18:13
  tell
• 18:13
  the
• 18:13
  full
• 18:13
  story
• 18:13
  because
• 18:14
  you
• 18:14
  also
• 18:14
  have
• 18:14
  to
• 18:15
  get
• 18:15
  their
• 18:15
  A1C
• 18:15
  and
• 18:16
  their
• 18:16
  lipid
• 18:16
  panel,
• 18:17
  and
• 18:17
  lo
• 18:17
  and
• 18:17
  behold,
• 18:17
  you
• 18:18
  might
• 18:18
  see
• 18:18
  that
• 18:18
  it's
• 18:18
  a
• 18:19
  wrecking
• 18:19
  ball
• 18:19
  for
• 18:19
  those
• 18:19
  things.
• 18:20
  So
• 18:20
  don't
• 18:20
  just
• 18:21
  assume
• 18:21
  if
• 18:21
  your
• 18:21
  patient's
• 18:22
  not
• 18:22
  gaining
• 18:22
  weight
• 18:22
  that
• 18:22
  their
• 18:22
  lipids
• 18:23
  aren't
• 18:23
  being
• 18:23
  dysregulated
• 18:24
  in
• 18:24
  some
• 18:24
  way,
• 18:25
  too.
• 18:25
  You
• 18:25
  have
• 18:26
  to
• 18:26
  make
• 18:26
  sure.
• 18:26
  But
• 18:27
  my
• 18:27
  greater
• 18:28
  point
• 18:28
  here
• 18:28
  is
• 18:29
  when
• 18:29
  you
• 18:29
  have
• 18:29
  depression
• 18:30
  and
• 18:30
  you
• 18:30
  have
• 18:30
  an
• 18:30
  incomplete
• 18:31
  response
• 18:31
  and
• 18:31
  your
• 18:31
  patient
• 18:32
  is
• 18:32
  not
• 18:32
  in
• 18:32
  remission
• 18:33
  and
• 18:33
  they're
• 18:33
  still
• 18:33
  being
• 18:34
  functionally
• 18:34
  impaired,
• 18:35
  you
• 18:35
  can
• 18:35
  look
• 18:36
  at
• 18:36
  these
• 18:36
  receptors
• 18:36
  as
• 18:37
  ways
• 18:37
  to
• 18:37
  specifically
• 18:38
  target
• 18:38
  specific
• 18:39
  things.
• 18:39
  And
• 18:40
  when
• 18:40
  we
• 18:40
  talk
• 18:40
  about
• 18:40
  rumination,
• 18:41
  anxiety,
• 18:42
  that
• 18:42
  excess
• 18:43
  glutamatergic
• 18:44
  activity,
• 18:44
  we
• 18:45
  want
• 18:45
  to
• 18:45
  dampen
• 18:45
  that.
• 18:45
  And
• 18:46
  we're
• 18:46
  thinking
• 18:46
  5ht2a
• 18:48
  glutamatergic
• 18:49
  activity,
• 18:50
  5ht2a.
• 18:52
  And
• 18:52
  if
• 18:52
  you
• 18:52
  antagonize
• 18:53
  that,
• 18:53
  you're
• 18:54
  going
• 18:54
  to
• 18:54
  dampen
• 18:54
  the
• 18:55
  glutamater
• 18:55
  activity.
• 18:56
  That
• 18:56
  patient
• 18:56
  might
• 18:57
  not
• 18:57
  be
• 18:57
  as
• 18:57
  ruminative
• 18:58
  and
• 18:58
  anxious
• 18:59
  and
• 18:59
  restless.
• 19:00
  Lanzapine
• 19:01
  or
• 19:01
  Zyprexa
• 19:01
  is
• 19:01
  the
• 19:02
  best
• 19:02
  for
• 19:02
  that.
• 19:02
  At
• 19:02
  what
• 19:03
  expense?
• 19:04
  Seroquel
• 19:05
  is
• 19:05
  also
• 19:05
  great
• 19:05
  with
• 19:05
  that.
• 19:06
  Respiratory
• 19:06
  is
• 19:07
  a
• 19:07
  potent
• 19:08
  two
• 19:08
  antagonist
• 19:09
  as
• 19:09
  well.
• 19:09
  It
• 19:09
  is
• 19:09
  a
• 19:10
  calming
• 19:10
  effect.
• 19:10
  But
• 19:11
  remember,
• 19:11
  it
• 19:12
  also
• 19:12
  can
• 19:13
  elevate
• 19:13
  prolactin,
• 19:14
  cause
• 19:14
  sexual
• 19:14
  dysfunction
• 19:15
  because
• 19:15
  it's
• 19:15
  blocking
• 19:16
  dopamine
• 19:16
  and
• 19:17
  other
• 19:17
  important
• 19:18
  pathways.
• 19:19
  You
• 19:19
  have
• 19:19
  to
• 19:19
  be
• 19:20
  a
• 19:20
  little
• 19:20
  bit
• 19:20
  careful
• 19:21
  with
• 19:21
  this
• 19:22
  and
• 19:23
  know
• 19:23
  that
• 19:23
  there's
• 19:24
  trade
• 19:24
  offs
• 19:24
  for
• 19:24
  everything.
• 19:25
  Now
• 19:25
  what
• 19:25
  do
• 19:26
  we
• 19:26
  do?
• 19:26
  I
• 19:26
  think
• 19:26
  we
• 19:26
  got
• 19:27
  Matt
• 19:27
  to
• 19:27
  a
• 19:27
  better
• 19:27
  place.
• 19:28
  We're
• 19:28
  going
• 19:28
  to
• 19:28
  potentially
• 19:29
  start
• 19:29
  him
• 19:29
  on
• 19:29
  Seroquel.
• 19:30
  We're
• 19:30
  going
• 19:30
  to
• 19:30
  watch
• 19:30
  his
• 19:30
  weight,
• 19:31
  his
• 19:31
  A1C,
• 19:31
  his
• 19:32
  lipids,
• 19:32
  but
• 19:32
  we
• 19:33
  want
• 19:33
  to
• 19:33
  really
• 19:33
  stop
• 19:34
  that
• 19:34
  rumination
• 19:35
  and
• 19:35
  worry.
• 19:36
  We
• 19:36
  want
• 19:36
  to
• 19:36
  get
• 19:36
  him
• 19:36
  to
• 19:36
  sleep.
• 19:37
  The
• 19:37
  histamine
• 19:38
  blockade
• 19:39
  of
• 19:39
  Seroquel
• 19:40
  is
• 19:40
  potent
• 19:41
  and
• 19:41
  it's
• 19:41
  going
• 19:41
  to
• 19:41
  help
• 19:41
  him
• 19:42
  at
• 19:42
  least
• 19:42
  fall
• 19:43
  asleep.
• 19:44
  We
• 19:44
  have
• 19:44
  the
• 19:45
  5ht2
• 19:45
  a
• 19:46
  potent
• 19:47
  antagonism
• 19:48
  that's
• 19:48
  going
• 19:48
  to
• 19:48
  help
• 19:49
  reduce
• 19:49
  ruminative
• 19:50
  worry
• 19:50
  and
• 19:50
  the
• 19:50
  excess
• 19:51
  glutamatergic
• 19:51
  activity.
• 19:52
  These
• 19:52
  are
• 19:53
  great
• 19:53
  things
• 19:53
  for
• 19:53
  Matt,
• 19:53
  right?
• 19:54
  Definitely
• 19:55
  a
• 19:55
  good
• 19:55
  thing.
• 19:55
  I
• 19:55
  did
• 19:56
  mention
• 19:56
  there's
• 19:56
  other
• 19:57
  pathways
• 19:58
  to
• 19:58
  potentially
• 19:59
  make
• 20:00
  people
• 20:00
  feel
• 20:00
  better
• 20:01
  and
• 20:01
  fine
• 20:02
  tune
• 20:02
  their
• 20:02
  antidepressant
• 20:03
  response.
• 20:04
  We
• 20:04
  can't
• 20:04
  forget
• 20:05
  about
• 20:05
  D2
• 20:05
  receptors.
• 20:06
  You
• 20:07
  know,
• 20:07
  dopamine
• 20:07
  2
• 20:07
  receptors.
• 20:09
  So,
• 20:09
  you
• 20:09
  know,
• 20:09
  if
• 20:10
  you
• 20:10
  have
• 20:10
  something
• 20:10
  like
• 20:10
  Risperdal,
• 20:11
  they
• 20:12
  reduce,
• 20:13
  they
• 20:13
  antagonize
• 20:14
  D2.
• 20:14
  So
• 20:14
  when
• 20:14
  someone
• 20:15
  is
• 20:15
  manic
• 20:15
  or
• 20:16
  psychotic,
• 20:16
  blocking
• 20:17
  D2
• 20:18
  can
• 20:18
  actually
• 20:19
  result
• 20:20
  in
• 20:20
  a
• 20:20
  more
• 20:20
  calming
• 20:21
  presentation.
• 20:22
  Less
• 20:22
  manic,
• 20:23
  less
• 20:23
  agitated.
• 20:24
  But
• 20:25
  you
• 20:25
  have
• 20:25
  the
• 20:25
  risk
• 20:25
  of
• 20:26
  prolactin,
• 20:26
  increased
• 20:27
  sexual
• 20:27
  side
• 20:27
  effects.
• 20:28
  If
• 20:29
  you
• 20:29
  block
• 20:29
  D2
• 20:29
  too
• 20:30
  much,
• 20:30
  you
• 20:30
  have
• 20:30
  apathy.
• 20:31
  And
• 20:31
  now
• 20:31
  the
• 20:32
  patient
• 20:32
  looks
• 20:32
  almost
• 20:32
  depressed.
• 20:33
  It's
• 20:34
  not
• 20:34
  as
• 20:34
  simple
• 20:34
  as
• 20:35
  do
• 20:35
  we
• 20:35
  always
• 20:36
  antagonize
• 20:36
  because
• 20:37
  partial
• 20:37
  agonists
• 20:38
  like
• 20:38
  Abilify
• 20:39
  or
• 20:39
  Brexpripazole
• 20:40
  can,
• 20:40
  can
• 20:40
  stabilize
• 20:41
  dopamine.
• 20:41
  They
• 20:41
  add
• 20:42
  a
• 20:42
  little
• 20:42
  bit
• 20:42
  of
• 20:42
  signal
• 20:42
  when
• 20:43
  dopamine
• 20:43
  is
• 20:43
  low
• 20:44
  and
• 20:44
  they
• 20:44
  can
• 20:44
  even
• 20:45
  dampen
• 20:45
  it
• 20:45
  when
• 20:45
  it's
• 20:45
  too
• 20:46
  high.
• 20:46
  Hence
• 20:46
  the
• 20:46
  partial
• 20:47
  agonist.
• 20:47
  Hence
• 20:47
  that
• 20:47
  abilifies,
• 20:48
  kind
• 20:48
  of
• 20:49
  like
• 20:49
  a
• 20:49
  dimmer
• 20:49
  switch.
• 20:50
  So
• 20:50
  if
• 20:50
  you
• 20:51
  have
• 20:51
  a
• 20:51
  patient
• 20:51
  who
• 20:51
  doesn't
• 20:52
  have
• 20:52
  a
• 20:52
  lot
• 20:52
  of
• 20:52
  motivation
• 20:52
  or
• 20:53
  drive
• 20:53
  or
• 20:53
  their
• 20:53
  cognition's
• 20:54
  a
• 20:54
  little
• 20:54
  slow,
• 20:55
  adding
• 20:55
  a
• 20:55
  little
• 20:55
  Abilify
• 20:56
  as
• 20:56
  a
• 20:56
  partial
• 20:57
  agonist
• 20:57
  is
• 20:57
  going
• 20:57
  to
• 20:57
  make
• 20:58
  that
• 20:58
  dopaminergic
• 20:59
  tone
• 20:59
  a
• 20:59
  little
• 21:00
  bit
• 21:00
  better,
• 21:01
  a
• 21:01
  little
• 21:01
  bit
• 21:02
  stronger.
• 21:02
  Not
• 21:02
  all
• 21:02
  the
• 21:03
  way,
• 21:03
  but
• 21:04
  it's
• 21:04
  again
• 21:04
  going
• 21:04
  to
• 21:05
  kind
• 21:05
  of
• 21:05
  fine
• 21:05
  tune
• 21:05
  it
• 21:05
  where
• 21:06
  it's
• 21:06
  low.
• 21:06
  It's
• 21:06
  going
• 21:06
  to
• 21:06
  make
• 21:06
  it
• 21:06
  better
• 21:07
  so
• 21:08
  you
• 21:08
  can
• 21:08
  target
• 21:08
  D2.
• 21:09
  The
• 21:10
  good
• 21:10
  thing
• 21:10
  about
• 21:10
  Abilify
• 21:11
  is,
• 21:11
  although
• 21:11
  it
• 21:11
  can
• 21:12
  absolutely
• 21:12
  cause
• 21:13
  weight
• 21:13
  gain
• 21:13
  because
• 21:13
  it
• 21:13
  weakly
• 21:14
  antagonizes
• 21:14
  5ht
• 21:15
  2c,
• 21:16
  it
• 21:16
  doesn't
• 21:17
  antagonize
• 21:17
  it
• 21:18
  as
• 21:18
  intensely
• 21:18
  as
• 21:18
  Zyprexa
• 21:19
  does
• 21:19
  or
• 21:20
  as
• 21:20
  Seroquel
• 21:21
  does,
• 21:21
  you
• 21:21
  still
• 21:22
  could
• 21:22
  cause
• 21:22
  weight
• 21:22
  gain
• 21:22
  on
• 21:22
  Abilify.
• 21:23
  Some
• 21:24
  say
• 21:24
  it's
• 21:24
  weight
• 21:24
  neutral.
• 21:25
  In
• 21:25
  my
• 21:25
  experience,
• 21:25
  I've
• 21:25
  seen
• 21:26
  both
• 21:26
  things.
• 21:26
  I've
• 21:26
  seen
• 21:26
  a
• 21:26
  lot
• 21:26
  of
• 21:26
  weight
• 21:27
  gain
• 21:27
  on
• 21:27
  Abilify.
• 21:27
  I've
• 21:28
  seen
• 21:28
  no
• 21:28
  weight
• 21:28
  gain
• 21:28
  on
• 21:28
  Abilify.
• 21:30
  Either
• 21:30
  way,
• 21:30
  you
• 21:31
  can
• 21:31
  go
• 21:31
  a
• 21:31
  different
• 21:32
  path
• 21:32
  and
• 21:32
  still
• 21:32
  make
• 21:33
  the
• 21:33
  dopaminergic
• 21:34
  tone
• 21:34
  better.
• 21:34
  For
• 21:35
  people
• 21:35
  who
• 21:35
  have
• 21:35
  those
• 21:36
  cognitive
• 21:36
  motivation
• 21:37
  kind
• 21:37
  of
• 21:37
  sluggish
• 21:39
  symptoms
• 21:39
  that,
• 21:39
  that
• 21:40
  aren't.
• 21:40
  That
• 21:40
  haven't
• 21:41
  remitted
• 21:41
  yet,
• 21:41
  and
• 21:42
  bam,
• 21:42
  you
• 21:42
  target
• 21:42
  that
• 21:43
  D2
• 21:43
  receptor.
• 21:43
  And
• 21:44
  now
• 21:44
  that
• 21:44
  patient
• 21:45
  would
• 21:45
  be
• 21:45
  better.
• 21:45
  In
• 21:46
  this
• 21:46
  case
• 21:46
  with
• 21:46
  Matt,
• 21:47
  it's
• 21:47
  not
• 21:47
  his
• 21:47
  main
• 21:48
  problem.
• 21:48
  We
• 21:48
  talked
• 21:48
  about
• 21:49
  anxiety,
• 21:49
  rumination,
• 21:50
  and
• 21:50
  we're
• 21:51
  targeting
• 21:51
  5ht2a
• 21:52
  for
• 21:52
  that.
• 21:52
  But
• 21:53
  the
• 21:53
  D2
• 21:54
  is
• 21:54
  super
• 21:55
  critical
• 21:55
  in
• 21:56
  certain
• 21:56
  situations.
• 21:57
  D3
• 21:57
  is.
• 21:58
  D3
• 21:58
  receptors
• 21:59
  are
• 21:59
  concentrated
• 21:59
  in
• 21:59
  the
• 21:59
  mesolimbic
• 22:00
  and
• 22:00
  prefrontal
• 22:01
  regions,
• 22:01
  also
• 22:02
  tied
• 22:02
  to
• 22:02
  motivation
• 22:02
  and
• 22:03
  executive
• 22:03
  functioning.
• 22:04
  Now,
• 22:04
  Vraylar
• 22:04
  or
• 22:05
  cariprazine
• 22:05
  binds
• 22:06
  there
• 22:06
  with
• 22:06
  high
• 22:06
  affinity,
• 22:07
  and
• 22:07
  so
• 22:08
  it
• 22:08
  can
• 22:08
  be
• 22:08
  uniquely
• 22:09
  effective
• 22:09
  for
• 22:09
  anhedonia,
• 22:10
  apathy
• 22:10
  and
• 22:11
  cognitive
• 22:11
  fog.
• 22:12
  Just
• 22:12
  a
• 22:12
  little
• 22:13
  pearl
• 22:13
  there
• 22:13
  to
• 22:13
  keep
• 22:14
  in
• 22:14
  mind.
• 22:15
  So
• 22:15
  we
• 22:15
  talked
• 22:16
  about
• 22:16
  five
• 22:16
  HT1A,
• 22:17
  we
• 22:17
  talked
• 22:17
  about
• 22:17
  D2,
• 22:18
  we
• 22:18
  talked
• 22:18
  about
• 22:18
  D3,
• 22:19
  we
• 22:19
  talked
• 22:19
  a
• 22:19
  little
• 22:19
  bit
• 22:20
  about
• 22:20
  H1
• 22:20
  or
• 22:20
  histamine.
• 22:21
  And
• 22:22
  remember
• 22:22
  that
• 22:22
  these
• 22:22
  medications
• 22:23
  don't
• 22:23
  just
• 22:24
  act
• 22:24
  on
• 22:24
  one
• 22:24
  receptor.
• 22:25
  They
• 22:25
  have
• 22:25
  affinities
• 22:26
  for
• 22:26
  various
• 22:27
  different
• 22:27
  receptors.
• 22:28
  Each
• 22:29
  medication
• 22:29
  comparatively
• 22:30
  has
• 22:30
  different
• 22:31
  affinities
• 22:31
  for
• 22:31
  different
• 22:31
  receptors.
• 22:33
  Which
• 22:33
  medication
• 22:33
  is
• 22:34
  blocking
• 22:34
  histamine
• 22:35
  the
• 22:35
  most?
• 22:35
  AKA
• 22:36
  could
• 22:36
  cause
• 22:37
  sedation
• 22:37
  or
• 22:37
  even
• 22:37
  weight
• 22:38
  gain
• 22:38
  that
• 22:38
  way.
• 22:38
  Right.
• 22:39
  Which
• 22:39
  ones
• 22:40
  can
• 22:40
  cause
• 22:40
  orthostasis?
• 22:41
  The
• 22:42
  alpha
• 22:42
  adrenergic
• 22:43
  blockers.
• 22:44
  Right.
• 22:44
  So
• 22:44
  we've
• 22:44
  gotta
• 22:44
  look
• 22:45
  at
• 22:45
  that
• 22:45
  too.
• 22:46
  Alpha
• 22:46
  1
• 22:46
  and
• 22:46
  H1,
• 22:47
  Cyprexa
• 22:48
  and
• 22:49
  Quetiapine
• 22:50
  or
• 22:50
  seroquel.
• 22:51
  Hit
• 22:51
  those
• 22:51
  the
• 22:51
  hardest.
• 22:52
  They
• 22:52
  will
• 22:52
  help
• 22:52
  your
• 22:53
  patient
• 22:53
  go
• 22:53
  to
• 22:53
  sleep
• 22:54
  and
• 22:54
  might
• 22:54
  be
• 22:54
  effective
• 22:55
  on
• 22:55
  an
• 22:55
  inpatient
• 22:55
  ward,
• 22:56
  but
• 22:56
  at
• 22:56
  what
• 22:57
  cost?
• 22:57
  What
• 22:57
  does
• 22:57
  this
• 22:58
  patient
• 22:58
  have
• 22:58
  to
• 22:58
  do?
• 22:58
  What's
• 22:59
  their
• 22:59
  job
• 22:59
  look
• 22:59
  like?
• 23:00
  Is
• 23:00
  this
• 23:00
  daytime
• 23:01
  sedation
• 23:01
  going
• 23:01
  to
• 23:02
  be
• 23:02
  something
• 23:02
  they
• 23:03
  can
• 23:03
  manage?
• 23:04
  These
• 23:04
  are
• 23:04
  really
• 23:04
  important
• 23:05
  questions,
• 23:05
  and
• 23:06
  this
• 23:06
  is
• 23:06
  why
• 23:06
  it's
• 23:06
  not
• 23:06
  a
• 23:07
  one
• 23:07
  size
• 23:07
  fits
• 23:07
  all
• 23:08
  solution.
• 23:09
  You
• 23:09
  have
• 23:09
  to
• 23:09
  look
• 23:09
  at
• 23:09
  your
• 23:09
  patient,
• 23:10
  know
• 23:10
  who
• 23:10
  they
• 23:10
  are,
• 23:10
  what
• 23:11
  they're
• 23:11
  doing,
• 23:11
  and
• 23:12
  that's
• 23:12
  really
• 23:12
  going
• 23:13
  to
• 23:13
  get
• 23:13
  you
• 23:13
  the
• 23:14
  best
• 23:14
  idea
• 23:14
  of
• 23:15
  how
• 23:15
  to
• 23:16
  go
• 23:16
  about
• 23:16
  this.
• 23:17
  So
• 23:17
  I
• 23:17
  hope
• 23:17
  you
• 23:17
  appreciated
• 23:18
  this
• 23:18
  episode.
• 23:18
  I
• 23:19
  loved
• 23:19
  it.
• 23:19
  It's
• 23:19
  one
• 23:19
  of
• 23:19
  my
• 23:20
  favorite
• 23:20
  ones.
• 23:20
  I
• 23:20
  even
• 23:21
  learned
• 23:21
  a
• 23:21
  lot
• 23:21
  here.
• 23:22
  I
• 23:22
  think
• 23:22
  that
• 23:23
  at
• 23:23
  the
• 23:23
  end
• 23:23
  of
• 23:23
  the
• 23:23
  day,
• 23:24
  the
• 23:24
  big
• 23:24
  takeaways
• 23:24
  are
• 23:25
  not
• 23:25
  that
• 23:25
  you
• 23:25
  memorize
• 23:26
  every
• 23:26
  receptor,
• 23:26
  although
• 23:27
  that
• 23:27
  really
• 23:27
  does
• 23:27
  help
• 23:28
  you
• 23:28
  get
• 23:28
  more
• 23:28
  sophisticated
• 23:29
  about
• 23:29
  how
• 23:29
  you
• 23:30
  target
• 23:30
  things.
• 23:31
  I
• 23:32
  think
• 23:32
  the
• 23:32
  best
• 23:32
  thing
• 23:33
  to
• 23:33
  take
• 23:33
  in
• 23:33
  here
• 23:34
  is
• 23:34
  that
• 23:34
  your
• 23:34
  meds
• 23:35
  are
• 23:35
  doing
• 23:35
  multiple
• 23:36
  things
• 23:36
  at
• 23:36
  once,
• 23:36
  some
• 23:37
  good,
• 23:37
  some
• 23:37
  bad.
• 23:38
  And
• 23:39
  rather
• 23:39
  than
• 23:39
  look
• 23:40
  at
• 23:40
  the
• 23:40
  textbook
• 23:40
  definitions,
• 23:41
  rather
• 23:42
  than
• 23:42
  look
• 23:42
  at
• 23:43
  what's
• 23:43
  FDA
• 23:43
  approved,
• 23:44
  although
• 23:44
  you
• 23:44
  have
• 23:44
  to
• 23:44
  do
• 23:44
  that
• 23:45
  too,
• 23:45
  it's
• 23:46
  really
• 23:46
  good
• 23:46
  to
• 23:46
  look
• 23:46
  at
• 23:47
  your
• 23:47
  patient
• 23:47
  as
• 23:47
  a
• 23:47
  human
• 23:47
  and
• 23:48
  say
• 23:48
  what
• 23:49
  specific
• 23:49
  symptoms
• 23:50
  are
• 23:50
  still
• 23:50
  holding
• 23:51
  them
• 23:51
  back
• 23:51
  that
• 23:52
  have
• 23:52
  been
• 23:52
  incompletely
• 23:53
  treated.
• 23:54
  How
• 23:54
  do
• 23:54
  we
• 23:54
  get
• 23:55
  those?
• 23:55
  How
• 23:56
  do.
• 23:56
  How
• 23:56
  do
• 23:56
  we
• 23:56
  get
• 23:56
  those
• 23:56
  into
• 23:57
  a
• 23:57
  better
• 23:57
  place?
• 23:57
  And
• 23:58
  what
• 23:58
  agents
• 23:58
  am
• 23:59
  I
• 23:59
  using
• 23:59
  to
• 23:59
  do
• 23:59
  it?
• 24:00
  Is
• 24:00
  it
• 24:00
  realistic
• 24:01
  that
• 24:01
  I
• 24:01
  can
• 24:02
  get
• 24:02
  my
• 24:02
  patient
• 24:02
  to
• 24:03
  remission
• 24:03
  with
• 24:03
  this
• 24:04
  same
• 24:04
  medication?
• 24:04
  Or
• 24:04
  do
• 24:05
  I
• 24:05
  need
• 24:05
  to
• 24:05
  bring
• 24:05
  in
• 24:06
  a
• 24:06
  different
• 24:06
  kind
• 24:07
  of
• 24:07
  receptor
• 24:07
  target
• 24:08
  to
• 24:08
  get
• 24:09
  my
• 24:09
  patient
• 24:09
  functioning
• 24:10
  again?
• 24:10
  Fantastic
• 24:11
  questions
• 24:11
  to
• 24:11
  ask.
• 24:12
  And
• 24:12
  in
• 24:12
  Matt's
• 24:13
  case,
• 24:13
  Seroquel
• 24:14
  tended
• 24:14
  to
• 24:14
  be
• 24:14
  the
• 24:15
  one
• 24:15
  for
• 24:15
  him.
• 24:15
  Now,
• 24:16
  if
• 24:16
  weight
• 24:16
  gain
• 24:16
  was
• 24:16
  a
• 24:17
  really
• 24:17
  big
• 24:17
  issue
• 24:17
  in
• 24:17
  his
• 24:18
  case,
• 24:18
  we
• 24:18
  probably
• 24:18
  wouldn't
• 24:19
  go
• 24:19
  to
• 24:19
  Seroquel.
• 24:20
  Right?
• 24:20
  We
• 24:20
  might
• 24:21
  have
• 24:21
  to
• 24:21
  look
• 24:22
  at
• 24:22
  other
• 24:22
  ways
• 24:22
  to
• 24:23
  potentially
• 24:24
  quiet
• 24:24
  his
• 24:24
  anxiety
• 24:25
  by
• 24:25
  targeting
• 24:26
  5ht1a,
• 24:27
  you
• 24:27
  know,
• 24:28
  potentially
• 24:28
  going
• 24:29
  the
• 24:29
  abilify
• 24:30
  route
• 24:30
  so
• 24:30
  that
• 24:30
  we're
• 24:30
  mitigating
• 24:31
  weight
• 24:31
  gain
• 24:31
  so
• 24:32
  we're
• 24:32
  not
• 24:32
  antagonizing
• 24:33
  5ht
• 24:33
  2c
• 24:34
  as
• 24:34
  strongly.
• 24:35
  So
• 24:35
  it's
• 24:35
  kind
• 24:35
  of
• 24:35
  an
• 24:36
  art
• 24:36
  and
• 24:36
  a
• 24:36
  science.
• 24:36
  You've
• 24:37
  got
• 24:37
  to
• 24:37
  really
• 24:37
  understand
• 24:37
  your
• 24:38
  patient.
• 24:38
  What
• 24:38
  are
• 24:38
  deal
• 24:38
  breaker
• 24:39
  symptoms
• 24:39
  to
• 24:39
  him?
• 24:40
  Could
• 24:40
  we
• 24:40
  roll
• 24:40
  the
• 24:40
  dice
• 24:41
  and
• 24:41
  start
• 24:41
  respiratory
• 24:42
  if
• 24:42
  sexual
• 24:42
  side
• 24:43
  effects
• 24:43
  are
• 24:43
  not
• 24:43
  a
• 24:43
  major
• 24:44
  issue
• 24:44
  for
• 24:44
  the
• 24:44
  patient
• 24:45
  and
• 24:45
  you
• 24:45
  know,
• 24:46
  we
• 24:46
  don't
• 24:46
  want
• 24:46
  as
• 24:46
  potent
• 24:47
  of
• 24:47
  a
• 24:47
  5ht
• 24:48
  2c
• 24:48
  block
• 24:49
  here,
• 24:49
  but
• 24:49
  again,
• 24:49
  it
• 24:49
  could
• 24:50
  still
• 24:50
  cause
• 24:50
  weight
• 24:50
  gain.
• 24:51
  Again,
• 24:51
  we're
• 24:52
  balancing
• 24:52
  these
• 24:52
  things
• 24:53
  right?
• 24:53
  We've
• 24:53
  got
• 24:53
  to
• 24:54
  figure
• 24:54
  this
• 24:54
  out
• 24:55
  and
• 24:55
  balance
• 24:55
  everything.
• 24:56
  So
• 24:56
  I
• 24:56
  hope
• 24:56
  you
• 24:56
  enjoyed
• 24:57
  this.
• 24:57
  Please
• 24:57
  don't
• 24:58
  forget
• 24:58
  to
• 24:58
  subscribe.
• 24:59
  This
• 24:59
  has
• 24:59
  gotten
• 25:00
  really
• 25:00
  popular
• 25:00
  really
• 25:01
  quickly,
• 25:01
  largely
• 25:01
  by
• 25:02
  word
• 25:02
  of
• 25:02
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• 25:02
  sharing
• 25:03
  in
• 25:03
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• 25:04
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• 25:04
  and
• 25:04
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• 25:05
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• 25:05
  fascinating
• 25:06
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• 25:06
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• 25:07
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• 25:07
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• 25:07
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• 25:08
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• 25:08
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• 25:17
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• 25:19
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• 25:19
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• 25:19
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• 25:19
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• 25:20
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• 25:20
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• 25:20
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• 25:20
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• 25:30
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• 25:30
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• 25:30
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• 25:30
  and
• 25:31
  please
• 25:31
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• 25:31
  us
• 25:31
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• 25:31
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• 25:32
  with
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• 25:32
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• 25:32
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• 25:33
  about
• 25:33
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• 25:33
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• 25:34
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• 25:34
  about
• 25:34
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• 25:34
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• 25:35
  That
• 25:35
  helps
• 25:35
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• 25:35
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• 25:36
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• 25:36
  Thank
• 25:36
  you
• 25:37
  all
• 25:37
  very
• 25:37
  much
• 25:37
  and
• 25:37
  see
• 25:38
  you
• 25:38
  next
• 25:38
  time.
• 25:38
  Signing
• 25:39
  off.
• 25:39
  Bye
• 25:39
  bye.