A black box warning predicating about increased risk of suicide in persons younger than 25 is required by FDA for all antidepressant medicications. Dualfold growth of the suicidal ideation and behavior in children and adolescents was observed by two independent groups of the FDA experts. 1.5-fold augmentation of suicidality was reported in the age group of 18–24 years old.

It was observed that suicide addiction in patients olden than 24 had been declined in a minor way while it had decreased in a great measure in group in the age of 65 and older. Donald Klein criticized that analysis. He suggested that suicidality (that is defined as suicidal ideation and behavior) should not be undoubtedly a good surrogate marker for completed suicide. He also supposed that antidepressant medications increasing suicidality might avert actual event of suicide. That supposal runs counter to current beliefs in which suicidal ideation has been in one-to-one correspondence with attempt of suicide in retrospective studies and with suicide in prospective studies.

Suicidality and Prozac

It is hard enough to study suicidal ideation and behavior in clinical trials due to their infrequency. The results of 295 trials of 11 antidepressants for psychiatric indications should be united by FDA experts in order to obtain statistically significant data and analyze them. Probability value of suicidality in children using Prozac amplifies in half as large again (those data are not statistically significant in view of paucity of cases). While it was reported about reduction of probability value of suicidality in adult patients taking Prozac around at one third (those data are statistically significant).

The UK Medicines and Healthcare products Regulatory Agency (MHRA) pursue similiar investigation. The experts of UK MHRA reported about1.5-fold augmentation of probability value of suicide-related events in the children and adolescents on Prozac therapy as opposed to placebo group. Those data also didn’t reach statistical significance. They assert that the rate of self-harm for adults taking Prozac is similar to placebo group while suicidal ideation decreased twice (statistically significantly data)

1. To reduce gradually dose of Prozac;
2. To replace Prozac with the other SSRI agent, in situations when gradual changes off the Prozac dose is ineffective.

It was proved in some double-blind controlled studies.

There were some blind trials where discontinue of antidepressant therapy for a short time (4–8 days) with further renewal has been studied. It was found out that the most severe side effects had been caused with interruption of paroxetine. Interruption of Zoloft therapy induced severe adverse effects but milder then paroxetine. Prozac showed the best tolerance in that study. Slow elimination of Prozac from the body can explain that result.

32% of members of Prozac discontinued group complain about new or worsened side effects versus 27%of patients who continued treatment in a longer, 6 week-long, blind discontinuation study. Significantly higher 5-7% rate of dizziness at weeks 4-6 and 4% rate of somnolence at week 2 were reported by the patients who had interrupted therapy. Long Prozac half-life in the body was proved with withdrawal symptoms, lasting for a long time. People reported about dizziness persisting to the end of the study

Nausea (22% vs 9% for placebo), insomnia (19% vs 10% for placebo), somnolence (12% vs 5% for placebo), anorexia (10% vs 3% for placebo), anxiety (12% vs 6% for placebo), nervousness (13% vs 8% for placebo), asthenia (11% vs 6% for placebo) and tremor (9% vs 2% for placebo)are the common adverse effects caused with Prozac and greatly differing from placebo therapy.

7% of patients taking Prozac in clinical trials reported about rash or urticaria, sometimes serious. Discontinuation of the Prozac therapy leaded to that side effect in 32% of those patients. There are some reports about several cases of complications developed in patients with rash. Vasculitis and lupus-like syndrome were observed in those cases. Those systemic events gave occasion to death.

Akathisia is a common side effect of Prozac . It is often accompanied by purposeless movements of the feet and legs, constant pacing, and marked anxiety. Akathisia usually appears after the beginning of the Prozac therapy or increase of the dose. Reducing of Prozac dose, discontinuation of drug or treatment with propranolol can remove or relieve akathisia symptoms. There are proves that akathisia and suicidal attempts are relative. It was reported that there were patients who had been feeling better after the withdrawal of Prozac , but relapsed severe akathisia symptoms after resumption of Prozac therapy. The development of the akathisia forced those patients to wish to make quietus and that it had brought back about their prior suicide attempts. Physician should describe symptoms of akathisia to patients and staff because of coupling of akathisia with suicide and the distress. More rarely, Prozac can cause side effects related with movement disorders such as acute dystonia and tardive dyskinesia.

Increase of rate of poor adaptation of newborns can be resulted with taking Prozac during pregnancy. Mothers having Prozac therapy shouldn’t breastfeed because Prozac was found in milk. Prozac is classified by the American Association of Pediatrics as a drug for which the effect on the breastfeeding baby is still unknown but may be of great importance.

Antihistamine diphenhydramine showed some antidepressant-like properties. That fact was known at that time. These scientists chose 3-phenoxy-3-phenylpropylamine (a compound structurally similar to diphenhydramine) as terminus a quo. Dozens of its derivatives have been synthesized by Molloy. A selective norepinephrine reuptake inhibitor Nisoxetine became a result of proving the physiological effects of those agents in mice.

Another Eli Lilly scientist, David Wong, trying to discover a derivative inhibiting only serotonin reuptake, suggested that series of laboratory researches dedicated to reuptake of serotonin, norepinephrine and dopamine should be prospected again. In May 1972 Jong-Sir Horng carrying out that test discovered agent which was named later Prozac. It acted as the most potent and effective selective inhibitor of serotonin reuptake of the series.

Lilly scientists claimed Prozac to be the first selective serotonin reuptake inhibitor (SSRI). But they had to issue a correction two years later,where they declared that zimelidine developed by Arvid Carlsson and colleagues had been the first SSRI.

In August 2001 Prozac patent of Eli Lilly expired that induced inflow of generic drugs onto the market. Eli Lilly rebranded Prozac as “Sarafem” for the treatment of premenstrual dysphoric disorder in attempt to reimburse loss caused with reduction of sales of Prozac in Eli Lilly.

FDA has approved Prozac as the treatment of major depression (MDD), obsessive compulsive disorder (OCD), bulimia nervosa and panic disorder. Prozac proved its efficacy for depression in 6-week long double-blind controlled trials where it also relieved anxiety and improved sleep. Prozac was more effective against placebo for the prevention of depression relapse when the patients, who originally responded to Prozac, were treated for a further 38 weeks. It was found out in placebo-controlled trials that Prozac therapy is effective both in geriatric and pediatric depression.

Physicians can prescribe Prozac for treatment OCD both in adults and children. As against to depression treatment higher doses of Prozac have been more effective in treatment of Obsessive–compulsive disorder. Prozac approved itself as perfect drug in treatment of patients suffering from panic disorder. Using Prozac therapy in such patients leads to exceeding reduction of frequency of panic attacks. Quantity of binge-eating and purging episodes of bulimia nervosa can be significantly decreased if Prosac is taken. It was proved that using placebo for the prevention of bulimia nervosa is not nearly as good as long-termed (year-long) Prozac treatment.

MAIN TYPES OF ANTIDEPRESSANTS

Prozac is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Prozac is approved for the treatment of major depression (including pediatric depression), obsessive-compulsive disorder (in both adult and pediatric populations), bulimia nervosa, anorexia nervosa, panic disorder and premenstrual dysphoric disorder
You should NOT use Prozac if:
• you are allergic to any ingredient in Prozac;
• you are taking or have taken a monoamine oxidase inhibitor (MAOI) (e.g., phenelzine), selegiline, or St. John’s wort within the last 14 days;
• you are taking a fenfluramine derivative (e.g., dexfenfluramine), an H1 antagonist (e.g., astemizole, terfenadine), nefazodone, pimozide, a serotonin norepinephrine reuptake inhibitor (SNRI) (e.g., venlafaxine), sibutramine, thioridazine, or tryptophan
Contact your doctor or health care provider right away if any of these apply to you.
What does my physician need to know prior I start to use Prozac?
You should tell about any of these conditions:
• if you are pregnant, planning to become pregnant;
• lactation;
• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement;
• if you have allergies to medicines, foods, or other substances;
• if you or a family member has a history of bipolar disorder (manic-depression), other mental or mood problems, suicidal thoughts or attempts, or alcohol or substance abuse;
• if you have a history of seizures, heart problems, liver problems, severe kidney problems, stomach or bowel bleeding, diabetes, or metabolism problems;
• if you are dehydrated, have low blood sodium levels, or drink alcohol;
• if you will be having electroconvulsive therapy (ECT)
What medicines may interplay with Prozac?
Some medicines may interact with Prozac. Tell your health care provider if you are taking any other medicines, especially any of the following:
• Anorexiants (e.g., phentermine), fenfluramine derivatives (e.g., dexfenfluramine), linezolid, MAOIs (e.g., phenelzine), metoclopramide, nefazodone, selegiline, serotonin 5-HT1 receptor agonists (e.g., sumatriptan), sibutramine, SNRIs (e.g., venlafaxine, St. John’s wort, trazodone, or tryptophan because severe side effects, such as a reaction that may include fever, rigid muscles, blood pressure changes, mental changes, confusion, irritability, agitation, delirium, and coma, may occur;
• Anticoagulants (e.g., warfarin), aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen) because the risk of bleeding, including stomach bleeding, may be increased;
• Diuretics (e.g., furosemide, hydrochlorothiazide) because the risk of low blood sodium levels may be increased;
• Tramadol because the risk of seizures may be increased;
• Cyclobenzaprine or H1 antagonists (e.g., astemizole, terfenadine) because severe heart problems, including irregular heartbeat, may occur;
• HIV protease inhibitors (e.g., ritonavir) because they may increase the risk of Prozac’s side effects;
• Cyproheptadine because it may decrease Prozac’s effectiveness;
• Aripiprazole, benzodiazepines (e.g., alprazolam), beta-blockers (e.g., propranolol), carbamazepine, clozapine, dextromethorphan, digoxin, flecainide, haloperidol, hydantoins (e.g., phenytoin), lithium, norepinephrine reuptake inhibitors (e.g., atomoxetine), phenothiazines (e.g., chlorpromazine, thioridazine), pimozide, propafenone, risperidone, tricyclic antidepressants (e.g., amitriptyline), or vinblastine because the risk of their side effects may be increased by Prozac
This may not be a complete list of all interactions that may occur. Also tell them if you smoke, consume alcohol or caffeine drinks, use illegal drugs. Some items may interplay with Prozac. Check with your health care provider before you start, stop, or change the dose of any medicine.
Prozac administration
Use Prozac as directed by your doctor. Check the label on the medicine for exact dosing instructions.
You should read MedGuide given to you by the pharmacist with each prescription and refill carefully.
Take Prozac orally with or without meals.Taking Prozac at the same time each day will help you remember to take it. Continue to take Prozac even if you feel well. Do not miss any doses. Do not suddenly stop taking Prozac without checking with your doctor. Side effects may occur. They may include mental or mood changes, numbness or tingling of the skin, dizziness, confusion, headache, trouble sleeping, or unusual tiredness. You will be closely monitored when you start Prozac and whenever a change in dose is made.
Missing a dose
If you miss a dose, take it as soon as possible. If it is almost time for your next dose, take only that dose. It is prohibited to take double or extra doses.
Side effects caused with Prozac
The following side effects that usually do not require medical attention:
• Anxiety;
• decreased sexual desire or ability;
• diarrhea;
• dizziness;
• drowsiness;
• dry mouth;
• increased sweating;
• loss of appetite;
• nausea;
• nervousness;
• indigestion;
• trouble sleeping;
• weakness.
You should report to your prescriber about those side effects as soon as possible:
• Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue);
• bizarre behavior;
• black or bloody stools;
• chest pain;
• confusion;
• exaggerated reflexes;
• excessive sweating;
• fast or irregular heartbeat;
• fever, chills, or sore throat;
• hallucinations;
• increased urination;
• joint or wrist aches or pain;
• loss of coordination;
• new or worsening agitation, panic attacks, aggressiveness, impulsiveness, irritability, hostility, exaggerated feeling of well-being, restlessness, or inability to sit still;
• persistent or severe ringing in the ears;
• persistent, painful erection;
• red, swollen, blistered, or peeling skin;
• seizures;
• severe or persistent anxiety or trouble sleeping;
• significant weight loss;
• stomach pain;
• suicidal thoughts or attempts;
• tremor;
• unusual bruising or bleeding;
• unusual hoarseness;
• unusual or severe mental or mood changes;
• unusual swelling;
• vision changes;
• worsening of depression.
What should I watch for while taking Prozac
You should not drive, use machinery or do anything that needs mental alertness until you know how Prozac affects you due to you may feel faintness. If you are an aged patient do not sit or stand up quickly to reduce the risk of faintness. Alcohol can make you more dizzy, increase flushing and rapid heartbeats. Avoid alcoholic drinks.
Check with your doctor before you use medicines that may cause drowsiness (e.g., sleep aids, muscle relaxers) while you are taking Prozac; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.
Several weeks may pass before your symptoms improve. Do NOT take more than the recommended dose, change your dose, or take Prozac for longer than prescribed without checking with your doctor.
Children and teenagers who take Prozac may be at increased risk for suicidal thoughts or actions. Adults may also be affected. The risk may be greater in patients who have had suicidal thoughts or actions in the past. The risk may also be greater in patients who have had bipolar (manic-depressive) illness, or if a family member has had it. Watch patients who take Prozac closely. Contact the doctor at once if new, worsened, or sudden symptoms, such as depressed mood; anxious, restless, or irritable behavior; panic attacks; or any unusual changes in mood or behavior, occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur.
Diabetes patients – Prozac may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.
Serotonin syndrome is a possibly fatal syndrome that can be caused by Prozac. Your risk may be greater if you take Prozac with certain other medicines (e.g., “triptans,” MAOIs). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.
If your doctor tells you to stop taking Prozac, you will need to wait for several weeks before beginning to take certain other medicines (e.g., MAOIs, nefazodone, thioridazine). Ask your doctor when you should start to take your new medicines after you have stopped taking Prozac.
Prozac may rarely cause a prolonged, painful erection. This could happen even when you are not having sex. If this is not treated right away, it could lead to permanent sexual problems such as impotence. Contact your doctor right away if this happens.
Caution is advised when using Prozac in CHILDREN; they may be more sensitive to its effects, especially increased risk of suicidal thoughts or actions.
Prozac should be used with extreme caution in CHILDREN younger than 7 years old; safety and effectiveness in these children have not been confirmed. Prozac may cause weight changes. CHILDREN and teenagers may need regular weight and growth checks while they take Prozac.
PREGNANCY and LACTATION: Prozac may cause harm to the fetus if it is used during the last 3 months of pregnancy. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Prozac while you are pregnant. Prozac is found in breast milk. Do not breast-feed while you are taking Prozac.
Prozac Storage
Store in a dry place at 20-25 degrees C (68-77 F).