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ADM8283 - SECTION 6: THE SSRIs

 

Prior to the introduction of Prozac in 1988 almost all psychotropic medications were discovered serendipitously. The SSRIs represent the first time in psychotropic medication where the goal of medication development was to target one neurochemical input system and create a specifically desired output.

This is a major breakthrough in psychophysiology which is a field very much in its infancy. I am convinced that 100 years from now mental health professionals will look back at us, the pioneers, and giggle as they discuss our use of agents that potentiated norepinephrine and serotonin in the treatment of depression.

It is my sense that even within our lifetimes the psychotropic treatment of psychiatric problems will continue to change dramatically. Before the end of the 80's, Prozac, Zoloft and Paxil were all introduced into the arena of antidepressant therapy. These medications offered great promise in making the treatment of depression vastly easier and more effective.

These medications promised a reduction in the severity of side effects and increased speed in reaching a therapeutic response. These medications had an emotional appeal to therapists and clinicians because of their remarkable lack of potential use in suicide.

The SSRIs were almost instantly embraced as the new standard because of these factors that represent improvements over the TCAs, particularly in terms of side effects. However, time and perspective have allowed us to look at their use more objectively.

As mentioned previously, these medications have their effect by blocking the reuptake of the neurotransmitter serotonin as it carries messages within the nervous system and have almost no effect on norepinephrine. Because depression seems to be related to both effects within the serotonin systems and within the norepinephrine system, how can we tell when an SSRI is going to prove to be the better medication, as opposed to a TCA?

As I mentioned earlier, the SSRIs are not as effective as the TCAs in treating classically presenting depression. It is my sense that the SSRIs are most effective in treating longstanding, chronic anxiety and are wonderful in treating anxiety driven psychiatric states that can lead to depression, and in certain atypical depressions. I like to view the target population as people who have had their nervous system "ratcheted up a notch or two."

This type of anxiety often leads to a variety of conditions for which the SSRIs are not accepted as the mainstay of treatment. These conditions include obsessive-compulsive disorder, eating disorders - especially bulimia - and social phobias.

In addition, many dysthymic patients, for instance, whose depression may be related to long-standing stress and anxiety that ultimately just wears them down, may be wonderful candidates for an SSRI medication. This is in keeping with my sense that the patient who is most likely to respond to SSRIs is the patient who comes to you feeling “overwhelmed.”

These people may report subjective depression; however, you as clinicians should recognize a difference between these people and the previously described classically depressed patient. It is my sense that these medicines “ratchet down the nervous system a notch or two.”

This understanding I have seen in my practice has also been supported by some studies comparing SSRI medications with the medications that work on the norepinephrine system. At least some studies show medications that work on the serotonin systems are superior in terms of calming anxiety symptoms, while medications that work on norepinephrine systems are superior in terms of decreasing retardation.

In broad terms, norepinephrine systems are more deeply involved in maintaining drive and the capacity for experiencing rewards. The retardation seen in deeply depressed people may therefore be related to an absence of drive and an absence of the capacity to experience anything as rewarding, hence motivating.

The systems involved in these two aspects of depression may be relatively parallel and independent. If research does ultimately show this to be true, it may offer a fair measure of explanation for why certain kinds of depression respond better to these different kinds of medication.

Given the complex nature of the chemistry involved, however, we must approach this question humbly and with eyes open, and still respond to the real patients before us with medication approaches that work in the real world, not in theory.

Certain atypical depressions do respond to SSRI medications. These are patients who present with increased sleep and appetite. The depressed patient who reports despondency and hopelessness and needs to sleep excessively, both at night and during the day with frequent naps, displays a sleeping pattern associated with depressions that will respond to the SSRIs. This patient will also usually be someone who eats to comfort himself.

The described syndrome such as in obsessive-compulsive disorder and bulimia and social phobia can be seen as responses to anxiety.

The SSRI medications seem to cut down the anxiety, therefore the depressive and/or behavioral response to the anxiety is also diminished. As an example, take the bulimic patient who would typically have a hostile conversation with her mother, during which the mother is intrusive and critical. This would lead to the anxiety-provoked response of eating for comfort, followed by the guilt of feeling the physical satisfaction of eating, then subsequent purging. The SSRIs tend to cut off this response.

The patient, with SSRI treatment, might be more likely to conclude a similar conversation thinking, “Gee, my mother is very intrusive and critical”, and go back about her business.

This illustrates perhaps a more important point about this medication. Not only does it allow patients to let previously provocative experiences “roll off their back,” it also helps the patient to objectify their feelings.

It is my sense that the real value of the SSRIs is not only in the treatment of anxiety-driven states, but - with the anxiety reduced - allowing the patient to take his or her feelings and observe them from a different perspective. I will always coach patients with these medications to examine their responses to situations and begin to understand the pattern of those responses themselves.

It is likely the patient will begin to have an increased ability to observe more objectively his/her typical response in various settings, and then begin to put together the common denominators of those circumstances. In that sense the SSRIs are an extremely valuable therapeutic tool.

This does have some implications that the SSRIs can be used electively with healthy but neurotic patients during the course of therapy for the purpose of self-observation. This dovetails nicely a use of modern psychotropics with classic psychodynamic therapy, and may allow the patient to develop a sense of oneself in a way to help give him/her some control of neurotic responses to emotional problems.

These medications are also very effective in the use of dissociative states. Dissociation is a defense mechanism that is very primitive, and generally occurs in people who have been traumatized during the first decade of their lives. Those persons who are traumatized during the first five to six years of their lives often develop the more severe varieties of this, including multiple personality disorder.

Dissociation can be triggered by emotionally provocative situations that force the patient into finding the emotional posture that is “correct” - one that is able to protect the patient from that emotional stimulus - in order to avoid having the main personalities deal with that situation themselves.

SSRIs, much like in the previous scenario involving the bulimic patient, allow the dissociative patient to see coping options other than those in their primitive bag of defense mechanisms. With the reduction in the level of anxiety, the situation is more controllable, and more tolerable.

SSRIs are also being examined for other uses that relate to their anxiety reducing abilities. Doctors are often tempted to use these medications "off-label" for disorders that are difficult to treat with other medications and psychotherapy. This must be done with great caution and with clear understanding of the risks and rewards involved.

As a cautionary note to this effect, it is very tempting to utilize SSRIs in children because of their safety and lack of side effects. Depression in children presents in very atypical ways, such as agitation, oppositionalism, and lack of focus, rather than the despondency that we classically see in adults. However, in children anxiety adds structure and to reduce anxiety with the use of an SSRI may lead to “disinhibition.

For example, if you or I as adults tended to be people who screamed at red lights and became agitated while waiting for the red lights to turn green, using an SSRI might allow us to say, “Gee, this red light will eventually turn green. Why should it upset me?”

However, in children imagine instead a teacher sternly saying, “Do your homework,” a line that fills the child with some fear and anxiety of the consequences of not doing the homework. The child whose anxiety has been lessened by SSRIs might now say, “Homework? Who cares?” This is disinhibition.

There are, of course, situations where SSRIs are typically used with children. For example, SSRIs are very effective against specific anxiety-driven states, such as obsessive-compulsive disorder or eating disorders.

Interestingly, when Prozac was first marketed, there was consideration of using it as a dietary agent because most of us, when nervous, tend to eat - as a way of feeling the physical comfort of being filled and thereby reducing anxiety. In fact, people who overeat do sometimes report a reduction in their eating when on Prozac.

However, people with anorexia eat less when they are anxious. Therefore, what might happen when you introduce an SSRI to these patients? When they are on the medication, they are less anxious, and they will tend to eat more.

The first time I gave Prozac to an adult who had anorexia as a young adolescent, he gained 20 pounds. This was baffling at the time, given the consideration of Prozac as a dietary agent. With perspective, however, this phenomenon makes sense.

In children who are anorexic, SSRIs are extremely helpful in reducing the anxiety associated with their perfectionism, and I have had almost universal success in using SSRIs to treat these children. Children with obsessive and disturbing thoughts also respond quite well to these medications.

And now we come to one of the important questions about SSRI medications. How does one begin to choose which SSRI to use?

In 1991, following the initial introduction of these medications, I was sitting at a conference with Dr. Phillip Ninan, who is a leading psychopharmacological researcher with the National Institute of Mental Health, and I asked him this same question. If Prozac, Zoloft and Paxil were all SSRIs that are supposed to do the same thing, how do you decide which one to use on a given patient?

Not to de-mystify the medical profession, but Dr. Ninan, whom I had known for some time, giggled and suggested that I draw a circle on the wall and make pie cuts in it, labeling those pie cuts Prozac, Zoloft and Paxil and, while standing halfway across the room, throw darts at the circle to determine which medication is given to which patient.

This was very much the state of understanding these medications at the time. It is this dilemma that has led to the next generation of researching SSRIs. In examining the effects of serotonin, we now understand that there are several different serotonin receptors in the areas of the brain reached by SSRI medications.

For those of you who know a little more about SSRIs, this is where all that 5HT2 and 5HT3 stuff comes in. (These are the medical names for serotonin receptor sites within the brain, which are catalogued with names like this. There are numerous names to keep track of: 5-HT.sub.1, 5-HT.sub.2 and 5-HT.sub.3, 5-HT.sub.4,which are further divided into at least 15 different subtypes, e.g., 5-HT.sub.1A, 5-HT.sub.1B, 5-HT.sub.1D, 5-HT.sub.1B and 5-HT.sub.1F. It's all a little confusing, but important because they do come into play with regard to SSRIs and side effects.)

Celexa was developed when a little more was known about these receptor sites and side effects, and is more selective in avoiding the stimulation of the 5HT2 and 5HT3 receptor sites.

The receptor site labeled 5HT2 seems to be the place where SSRI medications can cause akathisias and extrapyramidal side effects, whereas 5HT3 receptors are thought to be involved in nausea and diarrhea.

Using the knowledge about these receptor sites, Celexa was designed to help avoid these side effects. However, in clinical practice this medication does not appear to have lived up to all its hoped for promise in terms of avoiding side-effects.

Celexa also makes the claim of reducing sexual side effects that are seen in the other SSRIs, due to its new level of selectiveness in where it inhibits the reuptake of serotonin.

However, it is my sense that the sexual dysfunction is also related to the anti-anxiety effect of the medication. If these medications work by making things that cause anxiety less likely to cause anxiety, they also seem to make exciting things seem less exciting, such as sex.

As described with the disinhibition seen in children, sometimes these medications appear to cause complacency. Again, less response to anxiety, therefore less response to excitement.

This, then, is our practical overview to the SSRIs. We will take a look at the main SSRIs medications in more detail, but first let's take a look at our summary pages. Again, these have been formatted to allow for easy printing.

 

                                   Prozac Summary Page


Trade Name: Prozac (1987)....................Chemical Name: Fluoxetine
Antidepressant type: SSRI......... Usual Dosage: 20-80 mg/qd
Pill sizes and types: Capsules: 10 mg. - Grey and green; 20 mg. - White and green; also clear, colorless syrup solution in amber glass bottles where 5 mL = 20 mg.
How it Works: Selectively inhibits reuptake of serotonin in areas of the brain that control mood and anxiety.
Most Common Uses: Clients with depression with anxiety components. Also used to treat OCD, panic disorder, social phobia, phobias, bulimia, and pain management.
When Prozac is used as opposed to other medications: For patients with a family history of positive response to Prozac. For patients who, through trial and error with other medications, show best response to Prozac with fewest side-effects.
Side-effects: GI upset, jitteriness and nervousness, anxiety, insomnia, tremors, somnolence, dizziness, headache, chills, decrease in libido, rashes, excessive perspiration, abnormal dreams, weight loss, muscle and joint pain, painful menstruation.
Contraindications and cautions in use: Not to be taken in conjunction with Seldane, Hismonal, or Propulsid. Not to be taken with MAO medications. Anaphylactoid events (allergic responses) have been reported. Should be used with caution with patients with mania, as it will sometimes precipitate mania in these patients.
Comments: Of the SSRI medications, Prozac seems to create the most balanced response: effectiveness with low side-effects profile. Patients often report feeling "medicated" on the other SSRI medications, and less "medicated" on Prozac. Prozac, however, has a very long half-life. This makes it harder to move from Prozac to another SSRI medication, as a longer amount of time is required for Prozac to clear the system. This means it is easier to go from Paxil, Zoloft or Celexa to Prozac, than it is to go from Prozac to these other medications. Doctors, who may need to try several medications to find the one that works best, may therefore be inclined to try another medication first, then come around to Prozac. Prozac may also be used best with Wellbutrin, a medication that is used to reduce sexual side-effects found with SSRIs.

 

                                       Zoloft Summary Page


Trade Name: Zoloft (1993)..............................Chemical Name: Sertraline
Antidepressant type: SSRI......... Usual Dosage: 50-200 mg/qd
Pill sizes and types: Capsules: 50 mg. - White and orange; 100 mg - Orange
How it Works: Selectively inhibits reuptake of serotonin in areas of the brain that control mood and anxiety.
Most Common Uses: Clients with depression with anxiety components. Also used to treat OCD, panic disorder, and PTSD.
When Zoloft is used as opposed to other medications: When a more sedative effect is sought with clients; when panic disorder is present. Zoloft should probably be used first when the client has depression with overwhelming anxiety.
Side-effects: GI upset, agitation, spaciness, anxiety, insomnia, fatigue, somnolence, dizziness, headache, ejaculatory delay, tremor, skin rashes, excessive perspiration, anorexia.
Contraindications and cautions in use: No data available on combined use with MAO inhibitors, so it ought not be taken with MAO medications. Should not be added to medication regimen until other contraindicated medications have cleared metabolically, and other contraindicated medications should not be added until this has cleared system. Should be used with caution with patients with mania, as it will sometimes precipitate mania in these patients. It has not been established whether it is safe to take this medication during pregnancy or during lactation. Because there may be some sedative effect, caution should be taken with patients who operate dangerous equipment.
Comments: Has a more sedating effect than Prozac, but therefore is less likely to cause jitteriness. Many people experience a period of spaciness when they start this medication.

 

                                      Paxil Summary Page


Trade Name: Paxil (1992)......................................Chemical Name: Paroxetine
Antidepressant type: SSRI......... Usual Dosage: 20-50 mg/qd
Pill sizes and types: Bisected, oval, biconvex tablets: 20 mg. - Pink; 30 mg. - Blue
How it Works: Selectively inhibits reuptake of serotonin in areas of the brain that control mood and anxiety.
Most Common Uses: Clients with depression with anxiety components. Also used to treat OCD, panic disorder, social phobia.
When Paxil is used as opposed to other medications: Because Paxil has a short half-life and a reasonable side-effects profile, it is often used as a first attempt to treat depression for which SSRIs are most appropriate. The short half-life means it leaves the system more quickly, and allows the patient to quickly move to another medication if Paxil does not prove to be effective or if side-effects are not well tolerated. As with all SSRIs, it may be chosen if other family members have had good response to Paxil.
Side-effects: Nausea, dry mouth, insomnia, somnolence, dizziness, ejaculatory delay, tremor, excessive perspiration, headaches.
Contraindications and cautions in use: Not to be taken with MAO medications. Should not be added to medication regimen until other contraindicated medications have cleared metabolically, and other contraindicated medications should not be added until this has cleared system. Should be used with caution with patients with mania, as it will sometimes precipitate mania in these patients. It has not been established whether it is safe to take this medication during pregnancy. Should not be used during lactation. Should be administered with great caution to patients taking oral anti-coagulants.
Comments: Halfway between the more invigorating effects of Prozac, and the more sedating effects of Zoloft. Headaches appear to be a relatively frequent complaint of patients who use this medication.

 

                                   Celexa Summary Page


Trade Name: Celexa (1998)....................Chemical Name: Citalopram hydrobromide
Antidepressant type: SSRI......... Usual Dosage: 20-40 mg/qd
Pill sizes and types: Oval, white, scored, film covered tablet, both 20 and 40 mg.
How it Works: Selectively inhibits pre-synaptic re-uptake of serotonin in neurons of the brain, and particularly in areas of the limbic system. Minimal effects on norepinephrine mechanisms of the brain.
Most Common Uses: Clients with anxiety based depression.
When Celexa is used as opposed to other medications: For more lethargic patients who need the anti-anxiety effects of the SSRI, but who also require additional energy.
Side-effects: Nausea and flatulence, dry mouth, sleepiness, headache, anorexia, agitation, ejaculation disorders, sinusitis, increased perspiration, rash. May cause flu-like symptoms in some people. May cause abnormal dreaming. May activate manic phase in patients with bi-polar disorder. Small number of patients in trials experienced decreases in heart rate.
Contraindications and cautions in use: Not to be taken with MAO medications. Must not be added to medication regimen until other contraindicated medications have cleared metabolically, and other contraindicated medications should not be added until this has cleared system. It has not been established whether it is safe to take this medication during pregnancy or during lactation, or during the acute recovery phase for myocardial infarction. Safety for children under 18 has not been established. Should be used very cautiously in conjunction with 5-HT1 agonists.
Comments: Have seen a troubling disorientation and detachment in many patients on this medication. Because Celexa tends to be invigorating, it can cause a high degree of jitteriness. This medication may also cause fewer side sexual side effects than the other SSRIs. This medication is being replaced by the next generation of Celexa, known as Lexapro. Lexapro has been designed to retain the positive effects of Celexa, while removing part of the chemical molecule that may cause some of the negative side-effects. It is unclear whether the promise of this chemical design approach will prove to be fulfilled by this new medication.

 

                                      Lexapro Summary Page


Trade Name: Lexapro (2002).............Chemical Name: Escitalopram Oxalate
Antidepressant type: SSRI......... Usual Dosage: 5-20 mg/qd
Pill sizes and types: Film coated, white to off-white, round tablets: 5 mg.; 10 mg. - Scored; 20 mg. - Scored. Also available in an oral solution
How it Works: Selectively inhibits reuptake of serotonin in areas of the brain that control mood and anxiety.
Most Common Uses: Clients with depression with anxiety components. Also is being used off-label for eating disorders, panic disorder, social phobia.
When Lexapro is used as opposed to other medications: Like its chemically similar cousin, Celexa, it may be preferable for more lethargic patients who need the anti-anxiety effects of the SSRI, but who also require additional energy.
As with all SSRIs, it may be chosen if other family members have had good response to Lexapro or Celexa.
Side-effects: Nausea, constipation, insomnia, gastrointestinal discomfort, fatigue, sweating, somnolence, ejaculation disorder.
Contraindications and cautions in use: Not to be taken with MAO medications or in combination with Celexa. Must not be added to medication regimen until other contraindicated medications have cleared metabolically, and other contraindicated medications should not be added until this has cleared system. It has not been established whether it is safe to take this medication during pregnancy or during lactation, or during the acute recovery phase for myocardial infarction. Safety for children under 18 has not been established. There have been reports of adverse reactions in conjunction with use of the migraine medication Imetrex. There have been reports of adverse effects upon sudden discontinuation of Lexapro, so discontinuation must be handled carefully.
Comments: This medication is designed to replace Celexa. Lexapro has been designed to retain the positive effects of Celexa, while removing part of the chemical molecule that may cause some of the negative side-effects. It is unclear whether the promise of this chemical design approach will prove to be fulfilled by this new medication. Early research does not indicate a clear safety or therapeutic advantage over Celexa.


                                     Luvox Summary Page


Trade Name: Luvox (1994)..................................Chemical Name: Fluvoxamine
Antidepressant type: SSRI...................... Usual Dosage: 100-300 mg/qd
Pill sizes and types: Round, scored, white tablets, both 50 mg. and 100 mg.
How it Works: Selectively inhibits pre-synaptic re-uptake of serotonin in neurons of the brain, and particularly in areas of the limbic system. Minimal effects on non-epinephrine mechanisms of the brain.
Most Common Uses: Clients with depression and/or obsessive compulsive disorder.
When Luvox is used as opposed to other medications: This may be the most effective of the SSRIs for treating anxiety based depression concurrent with Obsessive-Compulsive Disorders.
Side-effects: Nausea and other gastrointestinal complaints, dry mouth, fatigue, nervousness, insomnia, agitation, headache, increased perspiration, weight gain. Abnormal ejaculation noted by patients with obsessive-compulsive disorder.
Contraindications and cautions in use: Not to be taken with MAO medications. Must not be added to medication regimen until other contraindicated medications have cleared metabolically, and other contraindicated medications should not be added until this has cleared system. Should be administered carefully with clients also taking lithium and tryptophan. Will exaggerate effects of alcohol and increase the level of alcohol induced impairment. It has not been established whether it is safe to take this medication during pregnancy or during lactation, or during the acute recovery phase for myocardial infarction. Safety for children under 18 has not been established.
Comments: While said to be more effective than other SSRIs for treatment of OCD, many patients report intolerable nausea as a side-effect. A high number of clients seen have had to discontinue due to this GI difficulty. Therefore, Luvox would only be considered as a choice for a client with OCD and depression for whom Prozac has not been an effective medication, and who is able to tolerate the side-effects.

 

Prozac is the first of these medications introduced. I, as one might expect with my anachronistic prescribing habits, tend to use Prozac more than the other medications.

Prozac appears to be the most invigorating (energy enhancing) of the SSRIs and therefore might be more effective in treating the atypical depressions as previously described. However, the invigorating effect can cause a jitteriness that makes it not as useful in treating panic disorders.

Again, I am most likely to use this medication for the anxiety disorders as described earlier, and do find it very helpful in those areas. Prozac’s disadvantage is in its long half-life. Using Prozac as an initial SSRI can be a problem because it is much easier to go from Paxil or Zoloft to Prozac than it is to go from Prozac to Paxil or Zoloft.

Prozac’s half-life is roughly three to six weeks. Therefore it takes a long time to clear one’s system. There is now early documentation that, because of its long half life, it is difficult to add a second SSRI due to what looks to be serotonergic overload that has actually been implicated in some deaths. (So perhaps the SSRIs are not so completely safe after all.)

Dosages of Prozac tend to be around 20 mg. A nice advantage of Prozac is that the new 10 mg. tablets are scored and this gives you great control of dosing. When using this medication for mild anxiety disorders, such as generalized anxiety disorder, dosages of 5 or 10 mg. may be very effective

Dosages for more difficult states such as OCD and dissociative disorders may be as high as 80 or 100 mg. Familial response to Prozac should also be a guideline in whether or not to choose this medication. In other words, if one family member is responding well to Prozac, don’t try another SSRI first. This is a principle that should be utilized with respect to the use of any SSRI medications: if a family member has responded well to that SSRI, try it first on the patient.

Zoloft seems to be the most effective of the SSRIs in treating panic disorder. It may not be unreasonable in panic disorder to utilize an anti-anxiety medication such as Ativan during the first week or two of the Zoloft therapy until Zoloft kicks in.

Like the rest of the SSRIs, Zoloft tends to be effective within 5 to 7 days of initiating therapy and like the rest of the SSRIs, Zoloft can cause some initial “spaciness” during the first 3 to 5 days of using this medication. It is important to warn patients regarding this initial spaciness, as many will feel disoriented and uncomfortable. However, this is almost invariably transient and never lasts more than 10 days.

If that sense of spaciness lasts more than 10 days then perhaps one is dealing with a more disorganizing process, such as a schizoid or schizotypal disorder. Zoloft does however seem to cause night sweats, which is possible in all the SSRIs; however, more prominent in Zoloft than the others, and diarrhea and nausea which is also possible in the other medications, though more seen in Zoloft.

Because Zoloft appears to be the most sedative of the SSRIs, while I tend to prescribe all the other SSRIs as morning medications, with Zoloft I will observe the patient’s response to the medication and roughly half will take it in the morning and half will take it at bedtime.

Why do I ask patients to take SSRIs in the morning? Well, for example, despite Prozac’s long half life, it is my sense that there are other metabolites that are not being measured that may create the true effect.

A patient once reported to me that “Gee, Doc, I found out that my boss was taking Prozac,” to which I asked how did he find that out. The patient replied, “Well, my boss is usually really nice and this one day he was in a really angry mood. Midway through the morning he smacked himself on the forehead and said, ‘Gee, I forgot to take my Prozac this morning.’ So he ducked into his office and took his Prozac and 20 minutes later was his old self.”

With almost all the SSRIs, half the patients taking them report if they miss one day of medication they notice an increase in anxiety. The other half appear to notice it after missing two days of the medication, which would contradict the sense that a medicine like Prozac would have a long effect over a period of time. (This is why I am skeptical about the use of Prozac on a weekly basis.)

Dosing Zoloft at 50 mg. appears to be the reasonable dose for most patients. Some patients can get away with taking Zoloft at 25 mg. for less severe panic disorders; however when using Zoloft to treat atypical depressions, dosages as high as 300 mg. can be tolerated and utilized.

I have also used Zoloft very successfully in treating sexual inhibitions. Ironically, here are medications that cause complacency and appear to reduce sexual drive. However, patients who are “extremely uptight” or inhibited with respect to their sexuality are often able to relax enough with the SSRIs to approach sex in a more adult and relaxed way.

Ironically, while the SSRIs appear to make it more difficult for men and women to reach climax, in men sometimes this is a side effect that can be utilized favorably to maintain erections for a longer period of time.

I tend to put Paxil as in between Prozac and Zoloft with respect to its invigorating qualities. Therefore, it is a reasonable medication to use in people who are not necessarily struggling with panic disorder or in the atypical depressions characterized by overeating and oversleeping.

Paxil tends to not quite cause the jitteriness of Prozac and therefore may be useful in anxiety disorders for that reason. Lately, advertising for this medication has been heavy and it is more likely to be requested than the others.

The side effect that appears most unique to Paxil is what I frequently will see patients describing extremely vivid dreams accompanied by anxiety from these dreams and a restless sleep. While my describing these side effects may be disjointed, I have tried to place under each of these the side effects that I would most likely see associated with each of them.

However, any of the side effects that come with any of the SSRIs can be seen with any of the other SSRIs. Paxil’s dosaging is similar to Prozac’s and, other than the fact that Paxil’s half-life is 3 to 6 days, it has a lot of similarities to that medication in its clinical use.

Luvox is said to be more effective than the other SSRIs in treating obsessive-compulsive disorder. While this may be true, I’ve tended to use very little Luvox myself due to the intolerable nausea that occurs when initially taking this medication.

While not wishing to appear ignorant, this side effect has been so intolerable that, out of the dozens of patients I have tried on Luvox, only two or three have continued with it due to the difficulties with the GI distress.

Dosing for Luvox appears to be a little higher than Prozac and Paxil, with dosages running between 50 and 100 mg. Again, while Luvox is not amongst my personal favorites, you should not be discouraged by clinicians who do insist on using it, as it does appear to have very useful aspects to it, especially when used for obsessive-compulsive disorder.

As mentioned earlier Celexa represents the next generation of SSRIs and medication development with the understanding of how the effect on secondary serotonin receptors is the cause of many side effects. Celexa is introduced with the promise of reducing such side effects, especially the sexual side effects.

Clearly I have used Celexa as a medication with excellent effect, especially secondarily in patients who have had difficulty tolerating Prozac, Paxil or Zoloft, or in patients for whom a familial response to Celexa exists. What has been troublesome in my use of Celexa has been a persistent disorientation.

As noted earlier, all SSRIs seem to cause some sense of disorientation or “spaciness” during the first three days of use. Again, this is a very transient effect in most cases. However, in Celexa I have observed, and again this is my empirical observation only, that nearly half the patients I have put on Celexa report severe disorientation and even a sense of detachment.

When I have described this to some colleagues they have called this the “Minassian effect”, as not every clinician appears to see this.

Some have suggested that perhaps I have not made good choices as to whom I have prescribed this, as clearly SSRIs can provoke such responses in patients who tend to be more schizoid or schizotypal.

I imagine if I were doing that with Celexa, I would be doing it with all the other SSRIs, too, and have not seen that effect in the other SSRIs, so I don’t suspect that that’s a problem that only I have had. For example, patients have reported speaking and having the sense that the words they were saying were not the words they were thinking - and this was not a religious experience, or something occurring in a dissociative patient.

One highly intelligent professional, to whom I had prescribed Celexa at his request after treatment on Prozac, noted driving up and down a street that he had known quite well, trying to find a restaurant that he had visited on a dozen occasions. He spent an hour and one-half driving back and forth past the place without finding it, without even really realizing where he was.

Experiences like that have left this clinician less likely to use Celexa as a first line medication. Again, this is not to say that Celexa is not a good medication, and I am sure there are many very excellent psychiatrists who use Celexa with much more confidence than I do. That is just my personal experience. Again, dosaging Celexa appears to be similar to Prozac and Paxil.

At this point, there is a brand new addition to the Celexa family called Lexapro - the most recent SSRI. Any of you that may have taken organic chemistry might have some awareness that organic compounds, especially those with ring-like structures, tend to come with two connected parts, called isomers. There tend to be "left-handed" isomers and "right-handed" isomers, and the left-handed isomer is usually the biologically active one.

Lexapro has been produced from Celexa by processing the chemicals one additional step to eliminate the right handed isomer from the biologically active organic compound. The desired purpose for doing this was to reduce the side-effects that may be caused by the right-handed isomer. Despite favorable clinical trial data, and theories about the chemistry involved, I have not seen this bear out clinically.

It would, however, be reasonable to switch Celexa patients to Lexapro, as there would likely be no additional side-effects, and there may indeed be fewer side-effects. Because the biologically active side of the medication is the only part that is present, this means the dosage for Lexapro turns out to be half the equivalent dosage of Celexa.

This wraps up our section on the SSRI medications. I hope I have been helpful in clarifying the uses for these antidepressants. In our next section, we are going to take a look at one last group of antidepressants. This is the group of medications that have dual effects. Three of these work both on the serotonin systems - like the SSRIs - and upon the norepinephrine systems - like the TCAs. The fourth of these works on other important chemical systems, with sometimes very useful and promising effects. We will also work to provide some insights about the differences between them derived from a number of years of using these medications with real people.



Review Questions for Section VI

At this point in the training, you should be able to answer the following questions:

1. What aspect of depression does an SSRI medication best target, and how is this different than what the TCAs target?
2. What is the current thinking on SSRIs and overdose potential?
3. Is it true or false that a patient with atypical depression and sleep or appetite disturbances will likely do better with an SSRI medication?
4. What concerns exist about the use of SSRI medications in children?
5. Which SSRI medication appears to have the strongest sedative effects, and which appears to have the most invigorating or energy enhancing effects?
6. What is the relationship between Celexa and Lexapro?

 

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