Fluoxetine for Anxiety and Depression

Recruiting at 1 trial location

Overseen By Daniel S Pine, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: Psychoactive substances, SSRIs

Disqualifiers: ADHD, Tourette's, MDD, OCD, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 20 weeks

2530 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the relationship between certain brain functions and anxiety symptoms in children and teens. Participants will receive one of two treatments: cognitive behavioral therapy (CBT) or fluoxetine, a common medication for anxiety and depression. Researchers aim to understand how these treatments affect brain activity related to attention, memory, and motivation. Children and teens with ongoing anxiety symptoms, such as social phobia or generalized anxiety, might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I have to stop taking my current medications to join the trial?

Yes, you must stop taking any current psychoactive substances or medications to join the trial. The trial requires participants to be medication-free.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fluoxetine is generally safe for people. A study with over 9,000 patients found that fluoxetine is well-tolerated and effective for treating various mental health issues. Many individuals respond well to the usual dose of 20 mg per day.

The FDA has approved fluoxetine for treating conditions like depression and anxiety, indicating it has passed strict safety tests for these uses. People taking fluoxetine might experience mild side effects such as nausea, headaches, or trouble sleeping. These effects are common with many medicines and often subside over time.

In summary, fluoxetine is a well-researched drug with a strong safety record for treating anxiety and depression. It is important to consult a doctor about any concerns and to understand how it might affect each person individually. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about fluoxetine for anxiety and depression because it could enhance the effects of cognitive behavioral therapy (CBT). While standard treatments like SSRIs (including fluoxetine itself) and CBT are typically used separately, this approach combines them to potentially boost outcomes. The unique feature of this trial is administering fluoxetine immediately before CBT sessions, which might make the therapy more effective by priming the brain to better respond to CBT techniques. This method offers hope for faster and possibly more enduring relief from anxiety and depression symptoms.

What evidence suggests that this trial's treatments could be effective for anxiety and depression?

Research has shown that fluoxetine, an SSRI medication, effectively treats anxiety and depression. Data from 87 clinical trials involving over 9,000 patients indicate that fluoxetine is both safe and effective. Studies have found that it begins working fairly quickly, often within one to two weeks. Most people tolerate it well, experiencing no severe side effects. In children and teens, fluoxetine has reduced symptoms of anxiety and depression compared to a placebo. Overall, fluoxetine is a well-established treatment option for these conditions. Participants in this trial will receive cognitive behavioral therapy (CBT) and may also receive fluoxetine as part of the active treatment arm. ^{2 6 7 8 9}

Who Is on the Research Team?

Daniel S Pine, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

This trial is for children (8-17 years old) and adults (18-65 years old) with anxiety or major depression, who speak English and have an IQ over 70. It's not for those with serious medical conditions, pregnant women, or individuals currently on SSRIs or with certain psychiatric diagnoses like OCD or mania.

Inclusion Criteria

I have an anxiety disorder like social phobia or panic disorder that significantly affects my daily life.

I have been diagnosed with an anxiety disorder but don't have ongoing significant symptoms.

Exclusion Criteria

HEALTHY ADULT SUBJECTS: Any current psychiatric diagnosis

ALL SUBJECTS: Any serious medical condition or condition that interferes with fMRI or M/EEG scanning, and for patients electing medication, any condition that increases risk of SSRI treatment, Pregnancy, Current use of any psychoactive substance; current suicidal ideation; current diagnosis of attention deficit hyperactivity disorder (ADHD) of sufficient severity to require pharmacotherapy, Current diagnoses Tourette s Disorder, major depressive disorder (MDD); obsessive compulsive disorder (OCD), post-traumatic distress disorder, conduct disorder, Past or current history of mania, psychosis, or severe pervasive developmental disorder, Recent use of an SSRI with failure to respond or tolerate SSRI treatment at an adequate dose and duration, NIMH employees and staff and their immediate family members, History of any (excepting nicotine-related and cannabis-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo neuro-cognitive tasks, fMRI, and M/EEG to assess baseline neurocognitive features

4 weeks

1 visit (in-person)

Treatment

Participants receive cognitive behavioral therapy (CBT) for 12 weeks, with additional treatment in the final 8 weeks

20 weeks

Weekly visits (in-person)

Post-Treatment Assessment

Participants undergo post-treatment neuro-cognitive tasks, fMRI, and M/EEG to assess changes in neurocognitive features

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Attention Bias Modification Training
• Fluoxetine

Trial Overview The study tests how well Fluoxetine, an antidepressant medication, works alongside Attention Bias Modification Training to treat anxiety and depression in kids and adults. Participants will undergo fMRI scans before and after treatment to see if there are changes in brain activity related to mood improvement.

How Is the Trial Designed?

Group I: Active Experimental Treatment 2 Interventions

Subjects in both treatment arms receive cognitive behavioral therapy (CBT) for a 12-week period. In the final eight weeks of the trial, the subjects complete either the active-intervention arm or the control invention arm. In these arms, either the active or control treatment is administered immediately before a CBT session.

Group II: Control Placebo Group 1 Intervention

Subjects in both treatment arms receive cognitive behavioral therapy (CBT) for a 12-week period. In the final eight weeks of the trial, the subjects complete either the active-intervention arm or the control invention arm. In these arms, either the active or control treatment is administered immediately before a CBT session.

Fluoxetine is already approved in United States, European Union for the following indications:

Approved in United States as Prozac for:

• Depression
• Anxiety
• Obsessive-compulsive disorder
• Bulimia nervosa
• Panic disorder

Approved in European Union as Prozac for:

• Major depressive episodes
• Obsessive-compulsive disorder
• Bulimia nervosa

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

University of Oregon

Collaborator

Trials

91

Recruited

46,700+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Published Research Related to This Trial

Fluoxetine (Prozac) at a daily dose of 20 mg was rated by psychiatrists as having a moderate antidepressant effect, comparable to other antidepressants like amitriptyline and clomipramine, but with weak psychostimulant and anxiolytic effects.

The medication showed very weak sedative effects and lacked anticholinergic and hypotensive side effects, although moderate digestive side effects were noted, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assessment of the clinical activity of fluoxetin (Prozac) according of the "Stars of Liège" model]. Ansseau, M., Bataille, M., Bobon, D., et al.[2013]

In a study of 142 outpatients with major depression and anxiety, fluoxetine (20 mg/day) was found to be effective and safe, showing no increase in anxiety or agitation symptoms over 10 weeks of treatment.

While amitriptyline showed a quicker improvement in depression scores after 3 weeks, by the end of the trial, fluoxetine's effectiveness was comparable, indicating it is a viable treatment option for anxious depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is anxious-agitated major depression responsive to fluoxetine? A double-blind comparison with amitriptyline. Marchesi, C., Ceccherininelli, A., Rossi, A., et al.[2013]

Fluoxetine and its active metabolite, norfluoxetine, have long half-lives in rhesus macaques, with fluoxetine lasting 11-16 hours and norfluoxetine lasting 21-29 hours, indicating that they remain in the system for extended periods after administration.

A daily oral dose of 10 mg/kg of fluoxetine maintained serum concentrations within the therapeutic range observed in humans over 6 weeks, suggesting its potential effectiveness and the need for careful dosing in preclinical studies to avoid drug accumulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of fluoxetine in rhesus macaques following multiple routes of administration. Sawyer, EK., Howell, LL.[2022]

In a study of 22 first-episode, drug-naive patients with major depression and double depression, fluoxetine (20 mg daily) significantly reduced both depression and anxiety symptoms within just 10 days of treatment.

Patients with double depression showed a greater improvement in anxiety symptoms by day 50 compared to those with pure major depression, indicating fluoxetine's potential effectiveness in treating anxious depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine alone in the treatment of first episode anxious-depression: an open clinical trial. Spalletta, G., Pasini, A., Caltagirone, C.[2022]

Fluoxetine is a highly effective antidepressant that specifically inhibits serotonin reuptake, with an optimal dosage range of 20-40 mg daily, and has a low frequency of side effects, making it a safe option for treating major depression.

It has a long elimination half-life of 4 days after long-term use and is metabolized into an active form, norfluoxetine, which also inhibits serotonin reuptake, indicating a sustained therapeutic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine: a serotonin-specific, second-generation antidepressant. Sommi, RW., Crismon, ML., Bowden, CL.[2019]

In a study of 20 patients with HIV infection, fluoxetine treatment led to improvement in depression symptoms for 15 of the participants, indicating its efficacy in this population.

Fluoxetine was generally well tolerated among the patients, with no significant drug-drug interactions reported, suggesting it is a safe option for treating depression in individuals with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine treatment of depressed patients with HIV infection. Judd, FK., Mijch, AM., Cockram, A.[2017]

Fluoxetine is generally safe and well-tolerated for treating depression and other neuropsychiatric disorders, with common side effects primarily affecting the gastrointestinal and nervous systems at the recommended dose of 20 mg/day.

Its long half-life reduces the risk of withdrawal symptoms, but fluoxetine can interact with other medications due to its inhibition of certain liver enzymes, although most interactions are not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and side effect profile of fluoxetine. Wernicke, JF.[2022]

In a study of 234 cases of acute fluoxetine overdose, the majority of symptoms observed in adults were mild, including tachycardia, drowsiness, and tremors, indicating a generally low toxicity profile for fluoxetine.

The study concluded that symptoms from fluoxetine overdose are typically minor and short-lived, with aggressive supportive care being the only necessary intervention, suggesting a favorable safety profile for the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute fluoxetine overdose: a report of 234 cases. Borys, DJ., Setzer, SC., Ling, LJ., et al.[2022]

In a study of 106 cases of acute fluoxetine overdose, nearly half (48.6%) of patients who ingested fluoxetine alone remained asymptomatic, suggesting a relatively low toxicity profile for the drug in overdose situations.

Among those who did show symptoms, common issues included sleepiness and mild heart rate increases, indicating that while fluoxetine overdose can lead to some effects, it is generally considered to be benign compared to other overdoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fluoxetine in the overdose patient. Borys, DJ., Setzer, SC., Ling, LJ., et al.[2019]

A systematic review of 21 studies found that fluoxetine use during the first trimester of pregnancy does not significantly increase the risk of major fetal malformations, with an odds ratio of 1.12, indicating safety for the fetus.

However, there is a noted increased risk of cardiac malformations associated with fluoxetine use, with an odds ratio of 1.6 from cohort studies, suggesting that this risk may be influenced by factors such as ascertainment bias in reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fetal safety of fluoxetine: a systematic review and meta-analysis. Riggin, L., Frankel, Z., Moretti, M., et al.[2022]

A retrospective review of 44 fluoxetine exposure cases over one year found that overdose presents minimal risk of serious cardiovascular or neurological complications, with most cases being asymptomatic or experiencing mild symptoms.

Among the cases reviewed, no seizures were recorded, and adverse reactions were primarily linked to coingestants rather than fluoxetine itself, suggesting that fluoxetine is relatively safe even in overdose situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine ingestion: a one year retrospective study. Spiller, HA., Morse, S., Muir, C.[2022]

Fluoxetine, a selective serotonin reuptake inhibitor, was found to be significantly more effective in treating atypical depression characterized by negative affectivity, achieving a 91% efficiency in this group of 12 patients.

In contrast, fluoxetine showed only a 41% efficiency in patients with positive affectivity, and this group experienced more pronounced side effects, necessitating additional corrective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of fluoxetine (portal) in atypical depressions]. Andriushchenko, AV.[2022]

Fluoxetine has demonstrated antidepressant efficacy in major depression and may also be effective for a variety of other psychiatric conditions, including obsessive-compulsive disorder, anorexia nervosa, and Tourette's syndrome.

The pharmacological profile of fluoxetine suggests potential applications beyond depression, such as pain relief in diabetics and management of conditions like premenstrual syndrome and migraine headaches, although further controlled studies are needed to confirm these uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine: a spectrum of clinical applications and postulates of underlying mechanisms. Messiha, FS.[2019]

Fluoxetine, commonly known as Prozac, is the best-selling antidepressant worldwide, but its success is not necessarily due to superior efficacy; evidence suggests it offers only a modest improvement in tolerability compared to other treatments.

Despite its popularity, the overall effectiveness of fluoxetine and similar selective serotonin reuptake inhibitors (SSRIs) in treating depression has not shown significant advancements, raising questions about the true impact of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of achieving additional drug benefits at a reasonable cost. A review of the fluoxetine years. Freemantle, N., Mason, J.[2022]

Fluoxetine treatment for 8 weeks significantly reduced both depressive and anxiety symptoms in 123 outpatients with major depression and comorbid anxiety disorders, as evidenced by substantial decreases in Hamilton Rating Scale for Depression scores and other symptom scales.

Approximately 53% of patients responded to fluoxetine treatment, with 46% achieving remission, although those with comorbid obsessive-compulsive disorder showed lower response rates, indicating variability in treatment efficacy based on specific anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine treatment of depressed patients with comorbid anxiety disorders. Sonawalla, SB., Farabaugh, A., Johnson, MW., et al.[2017]

Citations

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Clinical efficacy and safety of fluoxetine in generalized ... The acting time of fluoxetine is relatively fast, within 1 or 2 weeks. In addition, fluoxetine was generally well-tolerated in short-term treatment with adverse ...

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A Double-Blind, Placebo-Controlled Clinical Trial of ... Specifically, fluoxetine, at a conventional 20-mg dose, was both safe and effective relative to placebo in this special population. Previous article in issue

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Depression Outcomes Among Patients Treated With ... Fluoxetine did not improve functional outcomes, but FOCUS and EFFECTS found that fluoxetine reduced the prevalence of depression. The pragmatic ...

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The unique role of fluoxetine in alleviating depression and ... The results showed that administration of each strain improved anxious or depressive behavior, as did fluoxetine, and vagotomy eliminated these effects. These ...

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Fluoxetine - StatPearls - NCBI Bookshelf Fluoxetine is an FDA-approved medication that has demonstrated efficacy in treating a spectrum of psychological conditions.

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Label for PROZAC (fluoxetine) - accessdata.fda.gov Safety of coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. PROZAC monotherapy is not indicated ...

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Adverse events and treatment discontinuations in clinical ... Data from this large series of clinical trials confirm that fluoxetine is well tolerated in the acute treatment of MDD in adults, especially at a dosage of 20 ...

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Fluoxetine: A Suitable Long-Term Treatment A review of fluoxetine's safety profile, especially during long-term treatment, is presented. Key safety advantages for fluoxetine include lower adverse ...