At first, that person should ask his\her physician if a special dose produced by some pharmaceutical companies and offered them as in the form of sample to doctors exists for the specific goal of discontinue.

If such a dose is not available, the main idea is that patient should try to decrease dosage gradually, in a smooth flowing manner. It is usually recommended to use half of the increments that health care provider would normally suggest for the process of discontinue in most people.

Pills

Patient should always carefully read leaflet of his\her drug to make sure that pills can be splitted. He\she can halve pills with help of pill splitter (it can be purchased for some dollars at the nearest pharmacy). This makes very easy to get half-arrow dosage of the original titration recommendation and take each step down for a week.

Capsules

Patient obviously can’t open them and take the contents raw…but dosage can still tapered off. Some empty gel caps should be purchased (just a couple bucks for a hundred). He\she should take a single daily dosage, open capsules and redistribute the medication into the empty gel caps to spread the total daily dosage into smaller increments. Each capsule should be rubbed before storage with a dry cloth to get any of the medication off of the outside of the capsule. A daily dosage amount should be gradually reduced, using each amount for a week.

That method showed a right spirit when discontinuing Paxil, one of the most notorious drugs for causing SSRI Discontinuation Syndrome. Doctor may acknowledge patient with the discontinuation problem and to give him\her helpful suggestions for reducing the discomfort. So, and the side effects were much more tolerable due to abovementioned method.

The main condition of minimizing of withdrawal symptoms is that the brain’s production of acetylcholine is not interrupted. Using food supplements containing choline, lecithin, and B complex is the easiest way to do it. Prerequisite levels of the neurotransmitter acetylcholine in the brain can be maintained with the B vitamins. Shortage of that neurotransmitter induces abstinence symptoms. Choline supplements or lecithin supplements (which are 13 percent choline) are also recommended because they are able to amplify the level of choline used by brain to produce acetylcholine during decreasing of dosage or discontinuing of antidepressant therapy.

Physician can suggest making dietary changes until the drug is not fully discontinued. A wide variety of foods contains lecithin and choline, but many of them are high also in cholesterol and fats. One of the best dietary sources of lecithin and choline is egg yolks. Beef steak, liver, organ meat, spinach, soybeans, cauliflower, wheat germ, peanuts, and brewer’s yeast also contain significant amount of dietary choline.

A lot of medicines (monoamine oxidase inhibitors, tricyclic antidepressants, antiparkinsonian agents, traditional antipsychotics, and clozapine.) acting on the central nervous system can lead to appearance of withdrawal syndrome symptoms. Condition known as rebound (an agitated state of emotion that occurs at the end of the dosage cycle, and lasts for 15-20 minutes, then disappears) was observed in some people. It happens when patient takes medications of short acting. Doctor can prescribe dietary modifications to solve that problem.

That phenomenon was voted as valid by psychiatric professional community. Notwithstanding that the symptoms can be different and have both physical and psychological origin, doctors are able now to detect patterns of SSRI abstinence syndrome.

Pharmacokinetic Differences Between Different SSRIs

nonlinear: half-life elimination is longer at higher plasma concentrations, due to autoinhibition of metabolism; Linear: half-life elimination does not depend on plasma concentration

After that one can experience severe symptoms. Headache, diarrhea, nausea, vomiting, cold fit, dizziness and fatigue, insomnia, agitation, impaired concentration, vivid dreams, depersonalization, irritability and suicidal thoughts are the most be widespread symptoms of withdrawal syndrome. Abovementioned symptoms can vary in wide range in intensity (from a total absence of to very severe) and time duration (from one to seven weeks) in different people.

It is induced with decreasing dosage or discontinuing of antidepressant medications. This phenomenon is known as SSRI discontinuation syndrome. It can become real Gehenna for the human creature.

One of its reasons is very short half-life of some SSRI medications. Very short half-life leads to absence of active metabolites that can help the drug to stay in the body for a long term. Such medications go in, last a few hours, and are excreted.

SSRIs are divided on two categories depending on their half-life: long acting and short acting. Prozac is a longer-acting SSRI while Paxil, Effexor, Zoloft and Luvox are short-acting. Decreasing dosage or discontinuing SSRIs with shorter half-life cause so-called anticholinergic rebound. That rebound is defined by an interruption in production of the key neurotransmitter acetylcholine which is used more when a person is under greater stress. The duration time of those symptoms varies in range from 1 to 7 weeks.

Symptoms of SSRI Discontinuation Syndrome

• Neurologic symptoms include:

  • Dizziness;
  • Vertigo;
  • Light headedness;
  • Difficulty walking

• Somatic (bodily) complaints include:

  • Nausea/vomiting;
  • Fatigue;
  • Headaches;
  • Insomnia

• Less common difficulties:

  • Shock-like sensations;
  • Parasthesia (skin crawling, burning or prickling);
  • Visual disturbances;
  • Diarrhea;
  • Muscle pain;
  • Cold fit

• Non-specific mental symptoms:

  • Shock-like sensations;
  • Agitation;
  • Impaired concentration;
  • Vivid dreams;
  • Depersonalization – sense of unreality and loss of self;
  • Irritability;
  • Suicidal thoughts

It was found out due to some double-blind controlled studies that 35-78% of patients who, after five weeks or more of treatment with the medication, abruptly had discontinued certain antidepressants or used 10mg increments or more, experienced one or more of the withdrawal symptoms. When antidepressant therapy had been renewed abstinency’s symptoms severity were ranged from mild-moderate in most patients, to extremely distressing in a small amount and have been lasting from one to seven weeks

It is instructive to consider the experience in general practice. One way to do this is to look at prescription records for a large number of patients and compare the doses initiated with how many remained on the medication for 4-6 months. The assumption is that if the doseis ineffective or intolerable the clinician will either raise the dose or stop the medication. This naturalistic experiment has been done with medicaid populations in California and Texas. The results are rather remarkable. About 90% of patients started on fluoxetine at 20mg/day remained on this dose at 6 month. On the other hand only about 25% of patients started on sertraline at 50mg/day (which is suggested as a therapeutic dose) remained on that dose for the entire 6 months. Frequently patients were switched to another antidepressant without the benefit of a trial of higher doses.

The implication is that a large number of clinicians do not feel comfortable titrating the sertraline. This creates a situation of prolonging the treatment trial in many patients. It would probably be better to start off with a drug and quickly titrate to a dose which is most likely to achieve remission.

Fluoxetine and paroxetine are metabolized substantially be the CYP-2D6 enzyme pathway this means there is the possibility for drug interactions with other agents which are metabolized through this system.

The use of these tables is only a guide to suspect potential drug interactions. You should always consult the prescribing information before prescribing any drug.

* identifies the side effects which may interfere with monitoring a depressive syndrome.

In excessive doses SSRI’s or when a second serotonergic agent is added a central serotonin syndrome may develop. In some cases such as when an MAOI is given along with the SSRI the effect may be fatal. Below is a list of the signs/symptoms of the central serotonin syndrome.

Central Serotonin Syndrome

Central Serotonin Syndrome

• Hyperthermia;
• Diaphoresis;
• Gastrointestinal distress;
• Mental Status changes;
• Myoclonus

Pharmacologic agents that inhibit 5HT uptake are generally considered antidepressants. An additional finding is that the antimanic agent, lithium, increases tryptophan availability. This suggests that serotonin functioning may be impaired in both mania and depression. A growing appreciation of the interactions of various neurotransmitters has resulted in a theory known as the permissive hypothesis.

The SSRIs mode of functioning

This theory explains a variety of findings such as the fact that lithium is effective in both the mania and the depressed phases of the bipolar disorder. This theory suggests that serotonin has a key role in determining whether changes in norepinephrine result in psychopathology. Simply put low serotonin permits the altered norepinephrine to ‘act’. If serotonin functioning and norepinephrine functioning are both low then the behavior is depressive. If serotonin is low and the norepinephrine is high the behavior is manic.

In addition, such reductions in 5-HIAA are also seen in patients with impulsivity.

A common sleep problem in depression is that of midnight awakenings and early morning awakening. Sleep EEG recordings show that this is the result of reduced slow wave sleep. Such reductions of SWS has been produced by methods that reduce 5HT centrally.

Evidence for role of serotonin in depression



• Post mortem studies- suicide victims have decrease 5HT and 5HLAA and 5HT receptors in brain;
• Plasma tryptophan is low in depressed phase and normalizes with recovery;
• Low 5HLAA in violent suicide victims and patients with impulsivity;
• Reduced slow wave sleep

A group of medicines known as the Selective Serotonin Reuptake Inhibitors (SSRIs) are of great concern in the treatment of depression during last 30 years. Those pharmaceuticals are result of numerous researches dedicated to development of antidepressant medications with high efficacy, minimal anticholinergic and adverse effects and good tolerance. 5 drugs classified as Selective Serotonin Reuptake Inhibitors are produced now. But there are amount of invention in those drugs that allows physician to choose a specific medicine depending on individuality of patient. Chemical structure of SSRIs is shown abovementioned picture. Good tolerance and few serious adverse effects are the most advantages of those medicines.
The common features of SSRIs include:
1. Little or no anticholinergic activity (clomipramine is the exception)
2. Wide therapeutic window, few cardiac effects, no arrhythmias, no orthostasis
3. Relatively safe in overdose, no seizures, no coma, no respiratory depression
4. Well tolerated
5. A flat dose response curve
6. Equal efficacy (one is not more effective than another as long as equi-therapeutic doses are compared)
7. Similar effects on cortical beta and 5HT-2 receptors