Post SSRI Sexual Dysfunction
Encyclopedia
Post-SSRI sexual dysfunction (PSSD) is a name given to a reported iatrogenic sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....

 caused by the previous use of selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

 (SSRI) antidepressants. While apparently uncommon, it can last for months, years, or sometimes indefinitely after the discontinuation of SSRIs. It may represent a specific subtype of SSRI discontinuation syndrome
SSRI discontinuation syndrome
SSRI discontinuation syndrome, also known as SSRI withdrawal syndrome or SSRI cessation syndrome, is a syndrome that can occur following the interruption, dose reduction, or discontinuation of SSRI or SNRI antidepressant medications...

. This condition has not been well-established or tested in the field of medicine.

Symptoms

One or more of the following sexual
Human sexuality
Human sexuality is the awareness of gender differences, and the capacity to have erotic experiences and responses. Human sexuality can also be described as the way someone is sexually attracted to another person whether it is to opposite sexes , to the same sex , to either sexes , or not being...

 symptoms attributed to PSSD after the discontinuation of SSRIs include:
  • Decreased libido
    Libido
    Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

  • Impotence or reduced vaginal lubrication
    Vaginal lubrication
    Vaginal lubrication is a lubricating fluid that is naturally produced in a woman's vagina. Vaginal lubrication or moistness is present at all times, but production increases significantly during a woman's sexual arousal in anticipation of sexual intercourse...

  • Difficulty initiating or maintaining an erection
    Erection
    Penile erection is a physiological phenomenon where the penis becomes enlarged and firm. Penile erection is the result of a complex interaction of psychological, neural, vascular and endocrine factors, and is usually, though not exclusively, associated with sexual arousal...

     or becoming aroused
  • Persistent sexual arousal syndrome
    Persistent sexual arousal syndrome
    Persistent Genital Arousal Disorder , originally called Persistent Sexual Arousal Syndrome and also known as Restless Genital Syndrome or Mempin Syndrome , results in a spontaneous, persistent, and uncontrollable genital arousal, with or without orgasm or genital engorgement, unrelated to any...

     despite absence of desire
  • Muted, delayed or absent orgasm
    Orgasm
    Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...

     (anorgasmia
    Anorgasmia
    Anorgasmia, or Coughlan's syndrome, is a type of sexual dysfunction in which a person cannot achieve orgasm, even with adequate stimulation. In males the condition is often related to delayed ejaculation . Anorgasmia can often cause sexual frustration...

    )
  • Reduced or no experience of pleasure during orgasm
    Orgasm
    Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...

     (ejaculatory anhedonia
    Anhedonia
    In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

    )
  • Premature ejaculation
    Premature ejaculation
    Premature ejaculation is a condition in which a man ejaculates earlier than he or his partner would like him to. Premature ejaculation is also known as rapid ejaculation, rapid climax, premature climax, or early ejaculation....

  • Weakened penile, vaginal or clitoral sensitivity
  • Genital anesthesia
    Anesthesia
    Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

  • Loss or decreased response to sexual
    Human sexuality
    Human sexuality is the awareness of gender differences, and the capacity to have erotic experiences and responses. Human sexuality can also be described as the way someone is sexually attracted to another person whether it is to opposite sexes , to the same sex , to either sexes , or not being...

     stimuli

Prevalence

The true prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

 of PSSD has yet to be determined, although published calls have been made for post-marketing epidemiological studies. It is known that SSRIs can cause various types of sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....

. Initial studies found that such side effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

 were reported in less than 10% of patients. When doctors have specifically asked about treatment-emergent sexual difficulties, some have found that they are present in up to 60% of patients. Spontaneous reporting methods are believed to result in lower reporting rates than targeted questions, either due to recall bias
Recall bias
In psychology, recall bias is a type of systematic bias which occurs when the way a survey respondent answers a question is affected not just by the correct answer, but also by the respondent's memory. This can affect the results of the survey. As a hypothetical example, suppose that a survey in...

 or stigma
Social stigma
Social stigma is the severe disapproval of or discontent with a person on the grounds of characteristics that distinguish them from other members of a society.Almost all stigma is based on a person differing from social or cultural norms...

 regarding sexual disfunction.

Study data

While sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....

 can be common while taking SSRIs, the problem of persistent dysfunction after discontinuation does not appear to be as frequent, or at least not as well-known. Emerging evidence suggests that such persistence in sexual disfunction may in fact be more common. Onset of sexual
Human sexuality
Human sexuality is the awareness of gender differences, and the capacity to have erotic experiences and responses. Human sexuality can also be described as the way someone is sexually attracted to another person whether it is to opposite sexes , to the same sex , to either sexes , or not being...

 problems often occurs during, and sometimes after, extended SSRI use but there have been reports of rapid onset as well. It appears as though the majority of people regain their sexual function after stopping SSRIs, but some do not, and are faced with the persistent symptoms of post-SSRI sexual dysfunction (PSSD). In one study in which patients with SSRI-induced sexual dysfunction were switched to the dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...

 antidepressant amineptine
Amineptine
Amineptine was developed by the French Society of Medical research in the 1960s. Under the trade-names is used as an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting...

, 55% still had at least some type of sexual dysfunction after six months compared to 4% in the control group treated with amineptine alone. In recent placebo controlled double-blind studies testing the efficacy of SSRIs for treating premture ejaculation, it has been noted that the ejaculation-delaying effect of the medications may last for months after discontinuation in a percentage of the trial participants.

Published reports

Three cases of hyposexuality following SSRI use and a fourth case describing genital anesthesia following SSRI use were described in 2006. A fifth case of similar findings was published in late 2007. In early 2008, three more cases were published in the Journal of Sexual Medicine
Journal of Sexual Medicine
The Journal of Sexual Medicine is a peer-reviewed scientific journal published by Wiley-Blackwell. It is the official journal for the International Society for Sexual Medicine and for the International Society for the Study of Women’s Sexual Health...

, selected from a Yahoo Group
Yahoo! Groups
Yahoo! Groups is one of the world’s largest collections of online discussion boards. The term Groups refers to Internet communication which is a hybrid between an electronic mailing list and a threaded Internet forum, in other words, Group messages can be read and posted by e-mail or on the Group's...

 composed of over 2800 PSSD sufferers. There have also been several published cases of Persistent Genital Arousal Disorder (PGAD) and premature ejaculation
Premature ejaculation
Premature ejaculation is a condition in which a man ejaculates earlier than he or his partner would like him to. Premature ejaculation is also known as rapid ejaculation, rapid climax, premature climax, or early ejaculation....

 that start and last long after withdrawal from SSRIs. These symptoms are quite different from, and should not be confused with, hypersexuality
Hypersexuality
Hypersexuality is extremely frequent or suddenly increased sexual urges or sexual activity. Hypersexuality is typically associated with lowered sexual inhibitions. Although hypersexuality can be caused by some medical conditions or medications, in most cases the cause is unknown...

.

Surveillance and reporting

To establish, monitor, and regulate causation of PSSD in individual patients, one approach in use by consulation-liaison psychiatrists is to assay measurable parameters of patient health (hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 levels, sexual functioning) with a survey or laboratory tests before and after administering a psychiatric drug, based on individual patient concern regarding each of the listed side effects. If PSSD develops, a correlation can be established between assay results and PSSD, guiding further treatment for the individual patient and others. A lack of education
Education
Education in its broadest, general sense is the means through which the aims and habits of a group of people lives on from one generation to the next. Generally, it occurs through any experience that has a formative effect on the way one thinks, feels, or acts...

 on drug side effects and the presence of clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

 in a patient who is a candidate for antidepressant therapy can combine to reduce the patient's ability to advocate for tests. Calls have been made for better informed consent
Informed consent
Informed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...

 regarding the possibility of permanent sexual dysfunction when prescribing SSRIs to potential patients. Post-administration reporting of side effects may provide useful data for development of new drugs and better inform patients of their risks. In The United States, adverse effects are reported with FDA forms, 3500 for optional use (patients can self-report using this form), and 3500A, for mandatory reporting.

Etiology

It is currently not known what causes PSSD. Fluoxetine (Prozac), the prototypical SSRI, is classified as a reproductive toxin by the Center for the Evaluation of Risks to Human Reproduction
Center for the Evaluation of Risks to Human Reproduction
The National Toxicology Program and the National Institute of Environmental Health Sciences established the NTP Center for the Evaluation of Risks to Human Reproduction in 1998 as an environmental health resource to the public and regulatory and health agencies...

 (CERHR), an expert panel at the National Institute of Environmental Health Sciences
National Institute of Environmental Health Sciences
The National Institute of Environmental Health Sciences is a part of the National Institutes of Health , which is in turn a part of the Department of Health and Human Services ....

 at the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

.

Animal studies

Experiments with rodents have shown that chronic
Chronic toxicity
Chronic toxicity is a property of a substance that has toxic effects on a living organism, when that organism is exposed to the substance continuously or repeatedly. Compared with acute toxicity.Two distinct situations need to be considered:...

 treatment with SSRIs at a young age results in permanently decreased sexual behavior that persists into adulthood and is similar to PSSD. These studies found reductions in both the rate-limiting serotonin synthetic enzyme, tryptophan hydroxylase
Tryptophan hydroxylase
Tryptophan hydroxylase is an enzyme involved in the synthesis of the neurotransmitter serotonin. TPH catalyzes the following chemical reactionIt employs one cofactor, iron.- Function :...

, in dorsal raphe
Nucleus raphe dorsalis
The dorsal raphe nucleus is located on the midline of the brainstem and is part of the raphe nucleus, consisting of the rostral and caudal subdivisions....

 and in serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 (SERT) expression in the cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

. It also appears as though PSSD might be transgenerationally inherited, at least in rodents, since maternal exposure to fluoxetine impairs sexual motivation in adult male mice. It is not known whether these findings in rodents recapitulates the human condition, but the long term neurobehavioral consequences may be similar.

Short-term effects

There are physiological changes while on SSRI's. It has been postulated that drugs can exert epigenetic effects.

Changes include reduced hypothalamic-pituitary-testis axis occurs(HPTA) function,, decreased testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 levels, reduced sperm counts, which showed marked improvement after discontinuation and reduced semen quality with damaged sperm DNA, which is reversible after discontinuation.

Long-term effects

Treatment with fluoxetine (Prozac) has been shown to cause persistent desensitization
Desensitization
Desensitization can refer to:* Desensitization * Desensitization * Desensitization * Desensitization of explosives, see Phlegmatized...

 of 5HT1A receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 after removal of the SSRI in rats. These long-term adaptive changes in 5-HT receptors, as well as more complex, global changes, are thought to be mediated through alterations of gene expression. Some of these gene expression changes are a result of altered DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 structure caused by chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

 remodeling, specifically epigenetic modification of histones and gene silencing
Gene silencing
Gene silencing is a general term describing epigenetic processes of gene regulation. The term gene silencing is generally used to describe the "switching off" of a gene by a mechanism other than genetic modification...

 by DNA methylation
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...

 due to increased expression of the methyl binding proteins MeCP2
MECP2
MECP2 is a gene that provides instructions for making its protein product, MECP2, also referred to as MeCP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels...

 and MBD1
MBD1
Methyl-CpG-binding domain protein 1 is a protein that in humans is encoded by the MBD1 gene. The protein encoded by MBD1 binds to methylated sequences in DNA, and thereby influences transcription. It binds to a variety of methylated sequences, and appears to mediate repression of gene expression...

. Altered gene expression and chromatin remodeling may also be involved in the mechanism of action of electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...

 (ECT).

Because described gene expression changes are complex, and can involve persistent modifications of chromatin structure, it has been suggested that SSRI use can result in persistently altered cerebral gene expression leading to compromised catecholamine
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...

rgic neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...

 and neuroendocrine
Neuroendocrinology
Neuroendocrinology is the study of the extensive interactions between the nervous system and the endocrine system, including the biological features of the cells that participate, and how they functionally communicate...

 disturbances, However, without detailed neuropsychopharmacological
Neuropsychopharmacology
Neuropsychopharmacology is an interdisciplinary science related to psychopharmacology and fundamental neuroscience...

, pharmacogenomic
Pharmacogenomics
Pharmacogenomics is the branch of pharmacology which deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with a drug's efficacy or toxicity...

 and toxicogenomic
Toxicogenomics
Toxicogenomics is a field of science that deals with the collection, interpretation, and storage of information about gene and protein activity within particular cell or tissue of an organism in response to toxic substances. Toxicogenomics combines toxicology with genomics or other high throughput...

 research, the definitive cause remains unknown.

Relationship to "chemical imbalance" theory

Some critics of SSRIs claim that the widely-disseminated television
Television
Television is a telecommunication medium for transmitting and receiving moving images that can be monochrome or colored, with accompanying sound...

 and print advertising
Advertising
Advertising is a form of communication used to persuade an audience to take some action with respect to products, ideas, or services. Most commonly, the desired result is to drive consumer behavior with respect to a commercial offering, although political and ideological advertising is also common...

 of SSRIs promotes an inaccurate message, oversimplifying what these medications actually do. Much of the criticism stems from questions about the validity of claims that SSRIs work by correcting chemical imbalances. Without tools to accurately measure neurotransmitter levels and to allow for continuous monitoring during treatment, it remains difficult to know if one is correctly targeting a deficient neurotransmitter (i.e. correcting an imbalance) or reaching a desirable level of a particular neurotransmitter. It has been argued that without this knowledge for each patient, SSRIs can actually cause chemical imbalances and abnormal brain states. One possible mechanism is by inhibition of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

rgic neurotransmission, resulting in described persistent sexual dysfunction.

Other drugs

Antipsychotics are also known to cause sexual dysfunction, especially because of their antagonist effects on D2
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...

 dopamine receptors, as well as H1, α1
Alpha-1 adrenergic receptor
The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...

 and α2
Alpha-2 adrenergic receptor
The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...

 antagonism.

Treatment

There is no known cure for PSSD, mostly because its etiology is still poorly understood. Possible treatment options for SSRI-induced sexual dysfunction have been reviewed theoretically.

According to a survey of psychiatrists, Wellbutrin (Bupropion) is the drug of choice for the treatment of SSRI-induced sexual dysfunction, although this is not an FDA-approved indication. Thirty-six percent of psychiatrists preferred switching patients with SSRI-induced sexual dysfunction to bupropion, and 43 percent favored the augmentation of the current medication with bupropion. A higher dose of bupropion (300 mg) may be necessary: a randomized study employing a lower dose (150 mg) failed to find a significant difference between bupropion, sexual therapy or combined treatment.

Community Groups

Groups have formed around PSSD to help support PSSD victims, raise awareness, and look for cures. These include the following internet forums.

PSSD collaborative research. A forum dedicated to collaborative research into PSSD (post SSRI sexual dysfunction).

SSRIsex Yahoo Group. A private forum for victims to share their personal stories about PSSD

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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