Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine (Prozac)

[Guest guest]

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that can

effect metabolism of Prozac or enhance its central action."

http://www.molecularbrain.com/content/4/1/12

http://www.sfgate.com/cgi-bin/blogs/wchung/detail?entry_id=84999

Prozac-induced brain changes linked to unstable behavior

Winston Chung

Child Psychiatrist

Clinicians sometimes choose medications based on unique

characteristics like side effect profiles. An example of this is

choosing a drug with a side effect of sedation and giving it at

night for someone who has difficulty with sleep.

Fluoxetine, also known by the brand-name Prozac, has often been

called an 'activating' drug. Due to this reputation, some

clinicians will consider it for patients with low energy or

schedule it for the morning, and others might avoid it in

patients who are highly anxious.

Drugs in the same class as fluoxetine, also known as SSRIs, are sometimes also avoided due to

concerns of causing a side effect known as a manic switch - which is when someone goes

from having symptoms of depression and low energy to having

increased energy, decreased need for sleep and elevated mood.

A new research study from Japan has demonstrated that chronic

treatment of adult mice with fluoxetine (Prozac) causes changes

to brain cells that were associated with day-to-day fluctuations

in activity levels as well as anxiety-related behaviors. The

study was published in the journal Molecular

Brain.

Dr. Katsunori Kobayashi is the lead author and he told me that

this work is the first to link a destabilization in behavior to

SSRI-induced neuronal plasticity. Plasticity is the ability of the brain

cell or neuron to change its connections and

interactions with other neurons. Previous research has

associated SSRI-induced plasticity with antidepressant effects.

The researchers gave fluoxetine at a higher and lower dose to

mice for 4 weeks. At first they noticed a slight decrease in

activity at both doses. After 2 weeks of treatment, the mice at

the higher dose started to show "marked day-to-day fluctuation

of activity levels that was accompanied by occasional switching

from hypoactivity to hyperactivity and vice-versa." This

destabilized activity was accompanied by increased

anxiety-related behaviors and could be observed up to 4 weeks

after withdrawal from fluoxetine.

At a cellular level, the authors noted that the behavioral

changes, including anxiety-related behaviors, were associated

with fluoxetine-induced adaptations in hippocampal granule

cells, which are specialized cells found in the brain.

They previously showed that fluoxetine could reverse the state

of maturation of hippocampal granule cells in adult mice. This

fluoxetine-induced plasticity or 'dematuration' causes the cell

to revert back to a juvenile state where it is doesn't work as

well with other specialized cells. In this study, the authors

noted that the behavioral and cellular effects persisted after

fluoxetine was discontinued. Dr. Katsunori reported that "the

dematuration can be observed 1 month after discontinuation, so

it is not readily reversible."

One of the obvious limitations to this study is the fact that

what happens in mice doesn't necessarily translate to humans.

Another limitation is the supratherapeutic dosing used in the

mice, 22mg/kg/day at the higher dose and even 14mg/kg/day at the

lower dose. In a 150 pound human, this would equal taking up to

1500 mg of Prozac per day and most people don't take more than

80 mg daily. It would also be considered quite a leap to

extrapolate a manic switch from "marked day-to-day fluctuation

of activity levels."

Despite these limitations, this study could help shed some

light on how these drugs affect our brains, and may provide a

potential neurobiological basis for why Prozac may be

'activating'.

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that

can effect metabolism of Prozac or enhance its central action."

Posted By: Winston Chung MD (Email)

| March 15 2011 at 05:04 PM

[Guest guest]

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that can

effect metabolism of Prozac or enhance its central action."

http://www.molecularbrain.com/content/4/1/12

http://www.sfgate.com/cgi-bin/blogs/wchung/detail?entry_id=84999

Prozac-induced brain changes linked to unstable behavior

Winston Chung

Child Psychiatrist

Clinicians sometimes choose medications based on unique

characteristics like side effect profiles. An example of this is

choosing a drug with a side effect of sedation and giving it at

night for someone who has difficulty with sleep.

Fluoxetine, also known by the brand-name Prozac, has often been

called an 'activating' drug. Due to this reputation, some

clinicians will consider it for patients with low energy or

schedule it for the morning, and others might avoid it in

patients who are highly anxious.

Drugs in the same class as fluoxetine, also known as SSRIs, are sometimes also avoided due to

concerns of causing a side effect known as a manic switch - which is when someone goes

from having symptoms of depression and low energy to having

increased energy, decreased need for sleep and elevated mood.

A new research study from Japan has demonstrated that chronic

treatment of adult mice with fluoxetine (Prozac) causes changes

to brain cells that were associated with day-to-day fluctuations

in activity levels as well as anxiety-related behaviors. The

study was published in the journal Molecular

Brain.

Dr. Katsunori Kobayashi is the lead author and he told me that

this work is the first to link a destabilization in behavior to

SSRI-induced neuronal plasticity. Plasticity is the ability of the brain

cell or neuron to change its connections and

interactions with other neurons. Previous research has

associated SSRI-induced plasticity with antidepressant effects.

The researchers gave fluoxetine at a higher and lower dose to

mice for 4 weeks. At first they noticed a slight decrease in

activity at both doses. After 2 weeks of treatment, the mice at

the higher dose started to show "marked day-to-day fluctuation

of activity levels that was accompanied by occasional switching

from hypoactivity to hyperactivity and vice-versa." This

destabilized activity was accompanied by increased

anxiety-related behaviors and could be observed up to 4 weeks

after withdrawal from fluoxetine.

At a cellular level, the authors noted that the behavioral

changes, including anxiety-related behaviors, were associated

with fluoxetine-induced adaptations in hippocampal granule

cells, which are specialized cells found in the brain.

They previously showed that fluoxetine could reverse the state

of maturation of hippocampal granule cells in adult mice. This

fluoxetine-induced plasticity or 'dematuration' causes the cell

to revert back to a juvenile state where it is doesn't work as

well with other specialized cells. In this study, the authors

noted that the behavioral and cellular effects persisted after

fluoxetine was discontinued. Dr. Katsunori reported that "the

dematuration can be observed 1 month after discontinuation, so

it is not readily reversible."

One of the obvious limitations to this study is the fact that

what happens in mice doesn't necessarily translate to humans.

Another limitation is the supratherapeutic dosing used in the

mice, 22mg/kg/day at the higher dose and even 14mg/kg/day at the

lower dose. In a 150 pound human, this would equal taking up to

1500 mg of Prozac per day and most people don't take more than

80 mg daily. It would also be considered quite a leap to

extrapolate a manic switch from "marked day-to-day fluctuation

of activity levels."

Despite these limitations, this study could help shed some

light on how these drugs affect our brains, and may provide a

potential neurobiological basis for why Prozac may be

'activating'.

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that

can effect metabolism of Prozac or enhance its central action."

Posted By: Winston Chung MD (Email)

| March 15 2011 at 05:04 PM

[Guest guest]

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that can

effect metabolism of Prozac or enhance its central action."

http://www.molecularbrain.com/content/4/1/12

http://www.sfgate.com/cgi-bin/blogs/wchung/detail?entry_id=84999

Prozac-induced brain changes linked to unstable behavior

Winston Chung

Child Psychiatrist

Clinicians sometimes choose medications based on unique

characteristics like side effect profiles. An example of this is

choosing a drug with a side effect of sedation and giving it at

night for someone who has difficulty with sleep.

Fluoxetine, also known by the brand-name Prozac, has often been

called an 'activating' drug. Due to this reputation, some

clinicians will consider it for patients with low energy or

schedule it for the morning, and others might avoid it in

patients who are highly anxious.

Drugs in the same class as fluoxetine, also known as SSRIs, are sometimes also avoided due to

concerns of causing a side effect known as a manic switch - which is when someone goes

from having symptoms of depression and low energy to having

increased energy, decreased need for sleep and elevated mood.

A new research study from Japan has demonstrated that chronic

treatment of adult mice with fluoxetine (Prozac) causes changes

to brain cells that were associated with day-to-day fluctuations

in activity levels as well as anxiety-related behaviors. The

study was published in the journal Molecular

Brain.

Dr. Katsunori Kobayashi is the lead author and he told me that

this work is the first to link a destabilization in behavior to

SSRI-induced neuronal plasticity. Plasticity is the ability of the brain

cell or neuron to change its connections and

interactions with other neurons. Previous research has

associated SSRI-induced plasticity with antidepressant effects.

The researchers gave fluoxetine at a higher and lower dose to

mice for 4 weeks. At first they noticed a slight decrease in

activity at both doses. After 2 weeks of treatment, the mice at

the higher dose started to show "marked day-to-day fluctuation

of activity levels that was accompanied by occasional switching

from hypoactivity to hyperactivity and vice-versa." This

destabilized activity was accompanied by increased

anxiety-related behaviors and could be observed up to 4 weeks

after withdrawal from fluoxetine.

At a cellular level, the authors noted that the behavioral

changes, including anxiety-related behaviors, were associated

with fluoxetine-induced adaptations in hippocampal granule

cells, which are specialized cells found in the brain.

They previously showed that fluoxetine could reverse the state

of maturation of hippocampal granule cells in adult mice. This

fluoxetine-induced plasticity or 'dematuration' causes the cell

to revert back to a juvenile state where it is doesn't work as

well with other specialized cells. In this study, the authors

noted that the behavioral and cellular effects persisted after

fluoxetine was discontinued. Dr. Katsunori reported that "the

dematuration can be observed 1 month after discontinuation, so

it is not readily reversible."

One of the obvious limitations to this study is the fact that

what happens in mice doesn't necessarily translate to humans.

Another limitation is the supratherapeutic dosing used in the

mice, 22mg/kg/day at the higher dose and even 14mg/kg/day at the

lower dose. In a 150 pound human, this would equal taking up to

1500 mg of Prozac per day and most people don't take more than

80 mg daily. It would also be considered quite a leap to

extrapolate a manic switch from "marked day-to-day fluctuation

of activity levels."

Despite these limitations, this study could help shed some

light on how these drugs affect our brains, and may provide a

potential neurobiological basis for why Prozac may be

'activating'.

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that

can effect metabolism of Prozac or enhance its central action."

Posted By: Winston Chung MD (Email)

| March 15 2011 at 05:04 PM

[Guest guest]

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that can

effect metabolism of Prozac or enhance its central action."

http://www.molecularbrain.com/content/4/1/12

http://www.sfgate.com/cgi-bin/blogs/wchung/detail?entry_id=84999

Prozac-induced brain changes linked to unstable behavior

Winston Chung

Child Psychiatrist

Clinicians sometimes choose medications based on unique

characteristics like side effect profiles. An example of this is

choosing a drug with a side effect of sedation and giving it at

night for someone who has difficulty with sleep.

Fluoxetine, also known by the brand-name Prozac, has often been

called an 'activating' drug. Due to this reputation, some

clinicians will consider it for patients with low energy or

schedule it for the morning, and others might avoid it in

patients who are highly anxious.

Drugs in the same class as fluoxetine, also known as SSRIs, are sometimes also avoided due to

concerns of causing a side effect known as a manic switch - which is when someone goes

from having symptoms of depression and low energy to having

increased energy, decreased need for sleep and elevated mood.

A new research study from Japan has demonstrated that chronic

treatment of adult mice with fluoxetine (Prozac) causes changes

to brain cells that were associated with day-to-day fluctuations

in activity levels as well as anxiety-related behaviors. The

study was published in the journal Molecular

Brain.

Dr. Katsunori Kobayashi is the lead author and he told me that

this work is the first to link a destabilization in behavior to

SSRI-induced neuronal plasticity. Plasticity is the ability of the brain

cell or neuron to change its connections and

interactions with other neurons. Previous research has

associated SSRI-induced plasticity with antidepressant effects.

The researchers gave fluoxetine at a higher and lower dose to

mice for 4 weeks. At first they noticed a slight decrease in

activity at both doses. After 2 weeks of treatment, the mice at

the higher dose started to show "marked day-to-day fluctuation

of activity levels that was accompanied by occasional switching

from hypoactivity to hyperactivity and vice-versa." This

destabilized activity was accompanied by increased

anxiety-related behaviors and could be observed up to 4 weeks

after withdrawal from fluoxetine.

At a cellular level, the authors noted that the behavioral

changes, including anxiety-related behaviors, were associated

with fluoxetine-induced adaptations in hippocampal granule

cells, which are specialized cells found in the brain.

They previously showed that fluoxetine could reverse the state

of maturation of hippocampal granule cells in adult mice. This

fluoxetine-induced plasticity or 'dematuration' causes the cell

to revert back to a juvenile state where it is doesn't work as

well with other specialized cells. In this study, the authors

noted that the behavioral and cellular effects persisted after

fluoxetine was discontinued. Dr. Katsunori reported that "the

dematuration can be observed 1 month after discontinuation, so

it is not readily reversible."

One of the obvious limitations to this study is the fact that

what happens in mice doesn't necessarily translate to humans.

Another limitation is the supratherapeutic dosing used in the

mice, 22mg/kg/day at the higher dose and even 14mg/kg/day at the

lower dose. In a 150 pound human, this would equal taking up to

1500 mg of Prozac per day and most people don't take more than

80 mg daily. It would also be considered quite a leap to

extrapolate a manic switch from "marked day-to-day fluctuation

of activity levels."

Despite these limitations, this study could help shed some

light on how these drugs affect our brains, and may provide a

potential neurobiological basis for why Prozac may be

'activating'.

Dr. Katsunori stated that clinicians should be careful about

interpreting the behavioral effects of the drugs, but that their

results suggest that "Prozac may cause destabilized behavior" at

higher doses or "possibly in combination with other drugs that

can effect metabolism of Prozac or enhance its central action."

Posted By: Winston Chung MD (Email)

| March 15 2011 at 05:04 PM