Selective serotonin reuptake risks

Briggs G, Freeman R, Yaffe S Drugs in Pregnancy and Lactation A Reference Guide to Maternal and Fetal Risk. Philadelphia, Lippincott, Williams Wilkins, 2002 Chengappa KN, Kambhampati R, Perkins K, et al Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on neatment with selective serotonin reuptake inhibitor antidepressants. J Clin Psychiatry 62 503—508, 2001... 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

A number of non-hormonal therapies have been studied for symptomatic management of vasomotor symptoms, including antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs) and venlafaxine], herbal products (e.g., soy, black cohosh, and dong quai), and a group of miscellaneous agents (e.g., gabapentin, clonidine, and megestrol). The choice of therapy depends on the patient s concomitant disease states, such as depression and hypertension, and the risk for potential adverse effects. 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

Are Selective Serotonin Reuptake Inhibitors a Risk Factor for... 

SSRI = Selective serotonin reuptake inhibitor NSAID = Nonsteroidal anti-inflammatory drug CYP = cytochrome P-450 NAT2 = N-acetyl transferase type 2 J = Japanese C = Chinese A = African American. Poor metabolizers are not always at increased risk of ADR. 

When treating anxiety one should of course first treat any reversible medical condition. When pharmacological treatment is necessary SSRI is most often drug of choice. Selective serotonin reuptake inhibitors are both effective and safe. Benzodiazepines that have been widely used are drugs with a relative high risk of adverse effects (see Chapter 4). Risks for dependence and abuse must always be considered for benzodiazepines. 

Breggin, P. Suicidality, violence and mania caused by selective serotonin reuptake inhibitors (SSRIs) A review and analysis. Int J Risk Saf Med 2004 16,31-49. 

Haddad P (1998) The SSRI discontinuation syndrome. J Psychopharmacol 12 305-313 Healy D (2003) Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psychother Psychosom 72 71-79... 

Geriatric Considerations - Summary Bupropion has several advantages as an antidepressant agent for use in older adults. It has neither the anticholinergic or cardiac toxicities of the tricyclic antidepressants, and has fewer sexual side effects than selective serotonin reuptake inhibitors. Because this drug may lower seizure threshold, it should be used with caution in older adults with increased risk of seizures (e.g., previous stroke, early-onset Alzheimer s disease). 

DeBattista, C., Sofuoglu, M., and Schatzberg, A.F. (1998) Serotonergic synergism the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs. Biol Psychiatry 44 341—347. 

Tricyclic antidepressants are still prescribed today, but some patients experience side effects such as dry mouth, blurry vision, constipation, and other uncomfortable conditions. Other antidepressants have since been found that induce fewer side effects. One of the most popular is fluoxetine, which is marketed under the trade name Prozac. This drug, along with Zoloft and other antidepressants, are known to inhibit reuptake proteins specifically for serotonin. As a result, these drugs are called selective serotonin reuptake inhibitors, or SSRIs. Although some concerns have appeared because of a possible risk of suicide in young patients who take Prozac, these drugs are commonly prescribed and have proved highly effective in millions of patients. 

Antidepressants are as effective as benzodiazepines in the treatment of panic disorder. Moreover, antidepressants do not have the same risks of tolerance and dependency that are associated with benzodiazepine treatment. However, antidepressants take longer to work, so that significant improvement might not be observed until after a month of treatment. Although tricyclic antidepressants have been approved for the treatment of panic disorder, the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in its treatment has led them to become the favored treatment among antidepressant drugs. 

Dalton SO, Johansen C, Mellemkjaer L, et al Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding a population-based cohort study. Arch Intern Med 163 59-64, 2003... 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

Giner L et al Selective serotonin reuptake inhibitors and the risk for suicidality in adolescents An update. Int J Adolesc Med Health 2005 17(3) 211. [PMID 16231472]... 

Selective serotonin reuptake inhibitors (SSRIs) Increased risk of bleeding due to platelet inhibition. 

Spalletta G, Guida G, Caltagirone C. 2003. Is left stroke a risk-factor for selective serotonin reuptake inhibitor antidepressant treatment resistance J Neurol 250 449-455. 

Cronin-Fenton D et al (2010) Selective serotonin reuptake inhibitors and adjuvant tamoxifen therapy risk of breast cancer recurrence and mortality. Future Oncol 6 877-880... 

I warned the public and the health professions about the risk of SSRI antidepressant-induced suicidality in adults in Toxic Psychiatry (1991) and again in 1997 with a lengthy discussion in the first edition of this book. I elaborate in much greater detail on risk in 2003 in my scientific journal article Suicidality, Violence and Mania Caused by Selective Serotonin Reuptake Inhibitors (SSRIs) A Review and Analysis. ... 

Juurhnk, D., Mamdam, M., Kopp, A., 8c Redeimeier, D. (2006). The risk of suicide with selective serotonin reuptake inhibitors in the elderly. American Journal of Psychiatry, 163, 813-821. 

Estrogen is more effective than any other therapy in relieving vasomotor symptoms, and aU types and routes of systemic administration are equally effective in a dose-dependent fashion. If treatment can be tapered and stopped within 5 years, no evidence of increased risk of breast cancer is seen. Alternatives to estrogen for hot flushes are shown in Table 31-6. Progesterone alone may be an option in women with a history of breast cancer or venous thrombosis, but side effects limit their use. For women with contraindications to hormone therapy, selective serotonin reuptake inhibitors and venlafaxine are considered by some to be first-line therapy, but efficacy of venlafaxine beyond 12 weeks has not been shown. 

Aspirin produces an antipyretic and anti-inflammatory effect primarily by irreversibly inhibiting cyclooxygenase (thus having similar effects to NSAIDs). It possesses an antiplatelet effect that may have additive effect with other drugs with a similar effect (e.g, selective serotonin reuptake inhibitors) and those which affect other aspects of blood clotting. The risk of interactions and adverse effects are reduced by using a lower dose (e.g. 75 mg) fortunately, a full antiplatelet effect is seen at this dose. This is considered in Part 1, Cardiovascular Drugs. 

Simpson DA, Headley PM, Lumb BM (2008) Selective inhibition from the anterior hypothalamus of C- versus A-fibre mediated spinal nociception. Pain 136 305-312 Singh VP, Jain NK, Kulkarni SK (2001) On the antinociceptive effect of fluoxetine, a selective serotonin reuptake inhibitor. Brain Res 915 218-226 Sipe JC, Arbour N, Gerber A, Beutler E (2005) Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism possible risk for autoimmune disorders. J Leukoc Biol 78 231-238... 

St. John s wort also exhibits anti-inflammatory and antibacterial activity. Reports of antiviral activity arc unsubstantiated. The main adverse effect with St. John s wort is severe phototoxicity. A sunbum-like condition may occur at normal dosages. St. John s wort. should never be taken with MAOIs because of the risk of potentiation of the effects. Selective serotonin reuptake inhibitors (SSRIs) likewise should not be taken with St. John s wort because of the ri.sk of serotonergic syndrome. 

Hedenmalm K, Giizey C, Dahl M-L, et al. Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotnin and dopamine transporter and receptor polymorphisms. J Clin Psychopharmacol 2006 26 192-7. 

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