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Jenkins, 2016 Catastrophic Complications Related to Psychopharmacologic Drug Withdrawal


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#1 Vonnegutjunky

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Posted 17 August 2016 - 06:39 PM

Psychiatric Annals August 2016 - Volume 46 · Issue 8: 466-472 August 12, 2016

 

Catastrophic Complications Related to Psychopharmacologic Drug Withdrawal
James Jenkins, MD; Sean Glass, MD

 

James Jenkins, MD, is a Postgraduate Year-4 Resident, Massachusetts General Hospital/McLean Hospital Adult Psychiatry Residency Program; and a Clinical Fellow in Psychiatry, Harvard Medical School. Sean Glass, MD, is an Instructor in Psychiatry, Harvard Medical School and Massachusetts General Hospital.

Disclosure: The authors have no relevant financial relationships to disclose.

 

Abstract at http://www.healio.co...drug-withdrawal

Numerous physical and psychiatric effects can be attributed to the cessation of psychotropic medications, similar to those agents with abuse potential. In addition, drug withdrawal can exacerbate underlying psychiatric conditions and alter disease course and long-term outcomes. This article discusses specific withdrawal syndromes associated with several classes of psychotropic medications to increase prescriber awareness when tapering and discontinuing psychotropic medications, thereby facilitating discussions with patients about the risks of withdrawal. [ Psychiatr Ann . 2016;46(8):466-472.]

 

Full text:

A group of symptoms of variable clustering and degree of severity which occur on cessation or reduction of use of a psychoactive substance that has been taken repeatedly, usually for a prolonged period and/or in high doses. The syndrome may be accompanied by signs of physiological disturbance. 1

These syndromes are presumed to relate to the physiologic adaptations that include, but are not limited to, receptor density, sensitivity, and autoregulation, as well as to changes in neuro-connectivity that appear with prolonged exposure to a centrally acting drug. 2 The manifestations of withdrawal syndromes are thought to result from disruption of homeostasis created when a drug is removed and a new equilibrium needs to be achieved.

Given this relationship between changes in receptor levels and withdrawal symptoms, the withdrawal symptoms that are associated with specific classes of medications are predictable when placed in the context of their pharmacodynamics. In this article, we discuss the withdrawal symptoms associated with three major classes of psychotropic medications and address how knowledge of these drugs' mechanism of action can inform clinicians' predictions of withdrawal symptoms for those agents with less clearly researched withdrawal syndromes.

Sedative-Hypnotics

Because of their direct agonist effects, sedative-hypnotics most clearly show the interactions between drugs and receptors in the central nervous system (CNS) that lead to the emergence of withdrawal phenomenon. They also support the homeostasis disruption hypothesis for the genesis of drug-withdrawal syndromes.

Sedative-hypnotics exert their effects by modulating the brain's major neuroexcitatory pathway-the glutamate system. The excitatory effects of glutamate are balanced in the CNS by the inhibitory effects of the neurotransmitter gamma-amino butyric acid (GABA). GABA works by binding to GABA receptors on neurons and ultimately by decreasing the neuronal firing rate. 3 Despite subtle differences in where and how they activate receptors, sedative-hypnotics all function as GABA analogues. Like GABA, these drugs reduce neuronal firing, either by altering chloride ion influx (GABA-A receptor subtype) or via secondary messenger systems (GABA-B receptor subtype). It is this decrease in the neuronal firing rate that results in the anxiolytic, sedative, hypnotic, and anti-convulsant effects of these drugs. 3 Many therapeutic agents and illicit drugs interact with GABA receptors, but the most commonly prescribed ones in psychiatry are the benzodiazepines, "z-drugs" (eg, zolpidem), and barbiturates. Of these, benzodiazepines are, by far, the most prescribed and best-studied agents.

Prolonged use of benzodiazepines induces down-regulation of GABA-A receptors while triggering an increase in N-methyl-D-aspartate (NMDA) glutamate receptors in a regulatory feedback mechanism. This presumably occurs to "balance" excitatory and inhibitory neurotransmission systems. A new ratio of excitatory to inhibitory neural transmission is thus created to account for the addition of the GABA-ergic drug. Clinically, this process results in the tolerance to the effects of the medication that are observed with protracted use. When this balance is disrupted via rapid tapering or an abrupt discontinuation of medication, an excitatory neuronal surge results from excess glutamate acting on NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid receptors. Left unchecked, this results in the mild to severe glutamate- and hyperadrenergic-driven symptoms associated with benzodiazepine withdrawal. 4 Similar mechanisms and symptoms have been demonstrated for most other sedative-hypnotic drugs.

The most common symptom associated with discontinuation of a benzodiazepine is insomnia. 5,6 Other common symptoms of withdrawal include anxiety, restlessness, agitation, irritability, muscle tension, muscle aches, poor concentration, and impaired memory. 5-8 Less commonly, there may be an increased sensitivity to sound, light, touch, smell, and pain, as well as tremulousness, diaphoresis, palpitations, psychosis, confusion, and seizures. 6-8

Dreaded complications of benzodiazepine withdrawal (eg, psychosis, delirium, and seizures) are uncommon, occurring primarily in those with predisposing conditions (such as prior complicated withdrawal syndromes, seizures, or CNS pathology); these often arise after an abrupt discontinuation of high daily doses of benzodiazepines (>40 mg of diazepam-equivalents per day) 9,10 ( Table 1 ).

The timing of withdrawal symptoms is related to the individual pharmacokinetics of each of the benzodiazepines, with particular correlation to the half-life of the drug. After the abrupt discontinuation or dose reduction of short-acting benzodiazepines such as alprazolam, withdrawal symptoms typically begin within 12 to 24 hours and peak within 1 to 3 days; for longer-acting agents, such as diazepam, withdrawal symptoms may not emerge for 2 to 7 days, may not peak until 4 to 7 days, and may continue for 2 to 8 weeks or longer. 5,8,10

Of note, most benzodiazepines are metabolized in hepatocytes via the cytochrome P450 3A4 system. 9 In those with hepatic insufficiency, renal insufficiency, or dysfunction of other organs, metabolism of benzodiazepines may be reduced and their half-life increased. Clinicians should be aware that this may drastically delay the timing and course of withdrawal symptoms and the susceptibility to dreaded events such as seizures and delirium. In those with liver disease, oxazepam, temazepam, and lorazepam are preferred agents as they are metabolized by direct glucuronidation and not by oxidative metabolism (as are the remaining benzodiazepines), and thus their pharmacokinetics are less likely to become unpredictable.

Traditionally, short-acting benzodiazepines, such as alprazolam, have been associated with the most frequent and intense withdrawal syndromes. 7,8,10 However, a 2006 Cochrane review suggested that there is little direct support for this commonly held belief, as withdrawal symptom scores were similar in patients withdrawing from short-acting and long-acting agents. 11

Current guidelines for the pharmacologic management of benzodiazepine withdrawal in otherwise healthy adults typically include use (and then taper) of a long-acting benzodiazepine regardless of half-life of the initially prescribed medication. 5,11 However, key comparison studies with other agents are lacking, 12 and multiple strategies such as various benzodiazepine tapers, 5,10 phenobarbital taper, 12 and use of adjunctive carbamazepine 11,13 have been employed effectively. These studies suggest that, given the cross-tolerance and similar mechanism of action of drugs in the broader sedative-hypnotic class, treatment recommendations for benzodiazepine withdrawal can be extrapolated to other agents such as the barbiturates and z-drugs.

The WHO's 2009 Guidelines for the treatment of sedative-hypnotic withdrawal includes use of low doses (for patients taking <40 mg of diazepam-equivalents per day) and high doses (>40 mg of diazepam-equivalents per day). 5 In both strategies, patients are first stabilized on diazepam by converting their current sedative-hypnotic dose to diazepam-equivalents. The patient is continued on this dose in thrice daily doses for 4 to 7 days, and after that a gradual tapering strategy is initiated. 5

A retrospective analysis of benzodiazepine withdrawal (studying 310 patients treated over a 5-year period) showed that the use of a phenobarbital taper had significant efficacy and minimal adverse effects (the most common being sedation). 12 The recommended dosing schedule involved a 3-day oral taper of phenobarbital starting with a one-time dose of 200 mg, then 100 mg every 4 hours for 5 doses, then 60 mg every 4 hours for 4 doses, then 60 mg every 8 hours for 3 doses. Some patients received extra doses if they manifested persistent symptoms of withdrawal. This study supports the common clinical practice of substitution of various sedativehypnotics in the treatment of withdrawal.

Ultimately, the strategy used for treating withdrawal will depend on the patient's clinical status, including comorbid conditions, the clinical setting (eg, outpatient clinic, general hospital ward, intensive care unit), and other financial, institutional, and provider-specific considerations.

Antidepressants

Withdrawal syndromes have been documented for all classes of antidepressants. Case reports of antidepressant withdrawal first appeared in the psychiatric literature in 1959, shortly after the introduction of the first tricyclic-imipramine. 14 Antidepressant withdrawal syndromes are believed to result from a combination of decreased monoamine availability in synaptic clefts, changes in density of receptor types in different regions of the brain, and alterations in receptor sensitivity to available neurotransmitters (especially with muscarinic, histaminergic, and adrenergic receptors). 15 The mechanism for how withdrawal symptoms are produced is much less well-defined than with the sedative-hypnotics, because these drugs have a mix of indirect (via reuptake inhibition) and direct (via receptor agonism/antagonism) effects on CNS homesostasis. Nevertheless, it is the re-establishing of homeostasis that is thought to account for symptom production.

Although the exact prevalence rates are difficult to determine, prospective studies using the Discontinuation-Emergent Signs and Symptoms scale, a validated measurement of withdrawal symptoms, have found that at least one withdrawal symptom, across all antidepressants (ie, selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], monoamine oxidase inhibitors [MAOIs], and tricyclic antidepressants [TCAs]), is present in approximately one-third of patients. 16 As with sedativehypnotics, the prevalence and severity of withdrawal syndromes has also been shown to correlate with the drug's half-life ( Table 2 ). In a prospective, blinded study where antidepressant treatment was discontinued abruptly for 1 week, the prevalence of paroxetine-associated withdrawal symptoms was 55%, whereas it was only 30% for fluoxetine. 17

In observational studies, symptoms of antidepressant withdrawal emerged within 4 days of stopping the medication in 86% of patients and in 93% within the first 7 days. 18 As might be expected, withdrawal symptoms emerge sooner with drugs that have a shorter half-life. The duration of withdrawal symptoms is typically 1 to 3 weeks, with a median duration of 8 days. 18

There is significant overlap between the observed withdrawal symptoms associated with SSRIs and SNRIs. 19 Symptoms include nausea, lethargy, headache, electric shock-like sensations, dizziness with eye movement, ataxia, irritability, low mood, and sleep disturbance (usually insomnia and vivid dreams). 20 Dysequilibirum and sensory disturbances appear to be more common from SSRI/SNRI withdrawal than from withdrawal of other classes of antidepressants.

TCA withdrawal syndromes are driven primarily by a "cholinergic rebound syndrome." Symptoms of cholinergic rebound result from alterations in the muscarinic receptors after prolonged antagonism. Symptoms of cholinergic rebound and TCA withdrawal include nausea, vomiting, diarrhea, diaphoresis, insomnia, anxiety, and "flu-like" sensations. 21 TCAs are also unique among the antidepressants for their risk of inducing arrhythmias upon discontinuation.

Withdrawal from MAOIs is usually more impairing than seen with SSRIs, SNRIs, and TCAs. Although there is substantial overlap between withdrawal symptoms seen with MAOIs and all other classes of antidepressants, MAOI withdrawal has the added risk of being associated with delirium, paranoia, hallucinations, and severe depressive symptoms. 22

Less common reactions to antidepressant withdrawal include sudden-onset hypomania/mania, akathisia, and parkonsinism.

Guidelines for the management of antidepressant withdrawal are controversial. Schatzberg et al. 23 proposed guidelines that involved a gradual taper over abrupt discontinuation, reassurance when mild symptoms arose, and restarting the antidepressant at the lowest effective dose to ameliorate symptoms and then using a slow taper. Meta-analyses looking at gradual versus abrupt discontinuation failed to reliably demonstrate reduction of withdrawal symptoms with gradual reduction. Approaches to the management of more distressing withdrawal symptoms have included use of fluoxetine substitution (similar rationale to the use of diazepam for sedative-hypnotic withdrawal), benzodiazepines, and anticholinergic medications to reduce symptoms. Evidence for best practices for treatment of antidepressant withdrawal syndromes is lacking and treatment protocols remain pragmatic.

Antipsychotics

Similar to withdrawal from antidepressants, the withdrawal symptoms associated with antipsychotics appear to result from monoamine and receptor adaptations to drug exposure. Antipsychotics as a group, however, are more heterogeneous and complex in their pharmacodynamics. As a result, there are no similarly current or proposed diagnostic criteria for a unified antipsychotic withdrawal syndrome, and its prevalence rates are unknown. Most of what is known about antipsychotic withdrawal symptoms comes from retrospective reanalyses of trials like the Clinical Antipsychotic Trials of Intervention Effectiveness. 24

Each antipsychotic has varying degrees with which they interact with serotonergic, muscarinic, histaminergic, adrenergic, and dopaminergic receptors. Basic knowledge about relative affinities for each of these receptor types help clinicians predict a specific medication's side effects and, similarly, can be used to predict withdrawal symptoms ( Table 3 ). This type of approach is supported by both theoretical background and observational studies. 25

In general, the earliest withdrawal symptoms from antipsychotic discontinuation typically emerge within 1 to 4 days of abrupt discontinuation and tend to resolve within 2 to 3 weeks. 26 Early withdrawal symptoms are usually somatic and are related to rebound phenomena of previously antagonized receptors. For example, cessation of low-potency, highly anticholinergic, and antihistaminergic antipsychotics may result in rebound cholinergic symptoms and insomnia, respectively. As with withdrawal from TCAs, withdrawal symptoms associated with antipsychotics include myalgias, diaphoresis, malaise, rhinitis, nausea, vomiting, headaches, and increased anxiety. 26 These symptoms have been best described with chlorpromazine, but may also be expected with other lowpotency agents and the atypical antipsychotics (eg, olanzapine, quetiapine). 25,27

High-potency antipsychotics, characterized by their propensity for dopamine receptor blockade, best exemplify withdrawal symptoms unique to antipsychotics. Dopamine receptor blockade in the CNS has been shown to result in a post-synaptic "supersensitivity" of the receptor, particularly in the nigrostriatal and mesolimbic pathways. When antipsychotics are discontinued there is an abrupt increase in stimulation of these receptors by available dopamine that is thought to be responsible for rebound motor and psychotic symptoms. Motor symptoms include akathisia, dystonias, parkinsonism, and paradoxical worsening of tardive dyskinesia. 24,25,28 These motor disturbances can be transient or persistent, reversible or irreversible, and are also the best predictor of rebound psychosis. 24,25

"Supersensitivity" or rebound psychosis is defined by psychosis that emerges within the first 6 weeks after stopping an orally administered antipsychotic. 28 Rebound psychotic symptoms may also differ from those of prior psychotic episodes and respond more rapidly when the discontinued antipsychotic has been restarted. One meta-analysis found a prevalence of 25% in the first 6 weeks after abruptly stopping a typical antipsychotic, nearly double the rate when the antipsychotic was tapered gradually. 28

Clozapine is also associated with a withdrawal psychosis involving motor symptoms, despite its low affinity for dopamine D2 receptors. Clozapine is thought to induce these effects because, although it has a low D2 binding affinity, it rapidly dissociates and can repeatedly antagonize the receptor and therefore sensitize it. 29 Moreover, clozapine's strong muscarinic receptor antagonism is thought to potentiate the risk of rebound psychosis. Rates of psychosis in the first 7 days after abrupt clozapine discontinuation are as high as 13%. 28 Clozapine withdrawal is also associated with more significant symptoms of cholinergic withdrawal and it has been reported to lead to neuroleptic malignant syndrome, catatonia, and hyperthermia. 30 Withdrawal from olanzapine and quetiapine have many of the same manifestations as clozapine withdrawal, although the prevalence and severity seem to be much lower.

Little is known about the relationship between serotonin receptor subtypes and withdrawal symptoms. This makes it difficult to predict withdrawal syndromes for drugs with little effect on dopamine, histamine, and cholinergic receptors (eg, aripriprazole, lurasidone, and ziprasidone).

Given the heterogeneity of antipsychotic binding profiles, clinicians should be vigilant for the emergence of withdrawal symptoms (including psychosis) when switching from one antipsychotic to another, particularly when the agents used differ dramatically in their binding profile. There is a high risk of misattribution of these symptoms to the new medication.

As with antidepressants, there are no clear guidelines for management of antipsychotic-associated withdrawal symptoms. In general, the same approach is taken as with treating antidepressant withdrawal (provide a gradual taper schedule and supportive care). Some preliminary research has looked at the use of the anticonvulsants (eg, valproic acid, lamotrigine, gabapentin) for the treatment of severe supersensitivity motor and psychotic symptoms; however, definitive recommendations are lacking. 31

Conclusions

Although the specific nature of withdrawal symptoms differs based on the class of medication and receptor binding profiles, common principles apply across classes. Withdrawal symptoms can involve physical, neurologic, and psychologic features; they tend to be time-limited; and in almost all cases they appear to improve with slowing of the taper or with reintroduction of the discontinued medication. Patients should be warned about these symptoms and the clinician should be aware of their potential to emerge. The lack of clear guidelines for treatment of withdrawal symptoms is evidence for the need for further research in this area.

References
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2. World Health Organization. Neuroscience of psychoactive substance use and dependence. http://www.who.int/s...cience.pdf?ua=1. Accessed June 21, 2016.

3. Nestler EJ Hyman SE Holtzman DM Malenka RC. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience. 3rd ed. New York, NY : McGraw Hill ; 2015.

4. Vinkers CH Oliver B. Mechanisms underlying tolerance after long-term benzodiazepine use: a future for subtype-selective GABA(A) receptor modulators? Adv Pharmacol Sci. 2012 ; 2012 : 416864.

5. World Health Organization. Clinical guidelines for withdrawal management and treatment of drug dependence in closed settings. http://www.wpro.who....ines_forweb.pdf. Accessed June 21, 2016.

6. Lader M. Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol. 2014 ; 77 (2): 295 - 301. 10.1111/j.1365-2125.2012.04418.x

7. Schweizer E Rickels K. Benzodiazepine dependence and withdrawal: a review of the syndrome and its clinical management. Acta Psychiatr Scand Suppl. 1998 ; 393 : 95 - 101. 10.1111/j.1600-0447.1998.tb05973.x

8. Wright TM Cluver JS Myrick H. Management of intoxication and withdrawal: general principles. In: Herron AJ Brennan TK, eds. The ASAM Essentials of Addiction Medicine. 2nd ed. Philadelphia, PA : Wolters Kluwer ; 2015 : 251 - 255.

9. Owen JA. Psychopharmacology. In: Levenson JL, ed. The American Psychiatric Publishing Textbook of Psychosomatic Medicine. Washington, DC : American Psychiatric Publishing ; 2011 : 957 - 1020.

10. Alexander B Perry PJ. Detoxification from benzodiazepines: schedules and strategies. J Subst Abuse Treat. 1991 ; 8 ; 9 - 17. 10.1016/0740-5472(91)90022-3

11. Denis C Fatseas M Lavie E Auriacombe M. Pharmacological interventions for benzodiazepine mono-dependence management in out-patient settings. Cochrane Database Syst Rev. 2006 ;;(3): CD005194.

12. Kawasaki SS Jacapraro JS Rastegar DA. Safety and effectiveness of a fixed-dose phenobarbital protocol for inpatient benzodiazepine detoxification. J Subst Abuse Treat. 2012 ; 43 (3): 331 - 334. 10.1016/j.jsat.2011.12.011

13. Lader M Tylee A Donoghue J. Withdrawing benzodiazepines in primary care. CNS Drugs. 2009 ; 23 (1): 19 - 34. 10.2165/0023210-200923010-00002

14. Mann AM MacPherson AS. Clinical experience with imipramine in the treatment of depression. Can Psych Assoc J. 1959 ; 4 : 38 - 47.

15. Blier P Tremblay P. Physiologic mechanisms underlying the antidepressant discontinuation syndrompe. J Clin Psychiatry. 2006 ; 67 (Suppl 4): 8 - 13.

16. Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J Clin Psychiatry. 2006 ; 67 (Suppl 4): 14 - 21.

17. Rosenbaum JF Fava M Hoog SL Ascroft RC Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998 ; 44 : 77 - 87. 10.1016/S0006-3223(98)00126-7

18. Haddad PM Anderson IM. Recognizing and managing antidepressant discontinuation symptoms. Adv Psychiatr Treat. 2007 ; 13 : 447 - 457. 10.1192/apt.bp.105.001966

19. Black K Shea C Dursun S Kutcher S. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci. 2000 ; 25 : 255 - 261.

20. Fava GA Gatti A Belaise C Guidi J Offidani E. Withdrawal symptoms after SSRI discontinuation: a systematic review. Psychother Psychosom. 2015 ; 84 : 72 - 81. 10.1159/000370338

21. Dilsaver SC Kronfol Z Sackellares JC Greden JF. Antidepressant withdrawal syndromes: evidence supporting the cholinergic overdrive hypothesis. J Clin Psychopharm. 1983 ; 3 : 157 - 164. 10.1097/00004714-198310000-00031

22. Gahr M Schonfeldt-Lecuona C Kolle MA Freudenmann RW. Withdrawal and discontinuation phenomena associated with tranylcypromine: a systematic review. Pharmacopsychiatry. 2013 ; 46 : 123 - 129. 10.1055/s-0032-1333265

23. Schatzberg AF Blier P Delgado PL Fava M Haddad PM Shelton RC. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry. 2006 ; 67 (Suppl 4): 27 - 30.

24. Chouinard G Chouinard VA. Atypical antipsychotics: CATIE study, drug-induced movement disorder and resulting iatrogenic psychiatric-like symptoms, supersensitivity rebound psychosis and withdrawal discontinuation syndromes. Psychother Psychosom. 2008 ; 77 : 69 - 77. 10.1159/000112883

25. Cerovecki A Musil R Klimke A Withdrawal symptoms and rebound syndromes associated with switching and discontinuing atypical antipsychotics: theoretical background and practical applications. CNS Drugs. 2013 ; 27 : 545 - 572. 10.1007/s40263-013-0079-5

26. Dilsaver SC Alessi NE. Antipsychotic withdrawal symptoms: phenomenology and pathophysiology. Acta Psychiatr Scand. 1988 ; 77 : 241 - 246. 10.1111/j.1600-0447.1988.tb05116.x

27. Hollister LE Eikenberry DT Raffel S. Chlorpromazine in non-psychotic patients with pulmonary tuberculosis. Am Rev Resp Dis. 1960 ; 81 : 562 - 563.

28. Moncrieff J. Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal related-related relapse. Acta Psychiatr Scand. 2006 ; 114 (1): 3 - 13. 10.1111/j.1600-0447.2006.00787.x

29. Seeman P Tallerico T. Rapid release of anti-psychotic drugs from dopamine D2 receptors: An explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry. 1999 ; 156 : 876 - 884. 10.1176/ajp.156.6.876

30. Lee JWY Robertson S. Clozapine withdrawal catatonia and neuroleptic malignant syndrome: a case report. Ann Clin Psychiatry. 1997 ; 9 : 165 - 169. 10.3109/10401239709147792

31. Chouinard G. Severe cases of neuroleptic-induced supersensitivity psychosis. Diagnostic criteria for the disorder and its treatment. Schizophr Res. 1991 ; 5 : 21 - 33. 10.1016/0920-9964(91)90050-2

32. Physician's Desk Reference. http://www.pdr.net/browse-by-drug-name. Accessed July 22, 2016.

33. Stahl SM. Stahl's Essential Psychopharmacology Prescriber's Guide. New York, NY, Cambridge University Press ; 2014.


Edited by Altostrata, 17 August 2016 - 07:32 PM.
put in Journals format

Started 20mg Paxil 2006 due to postpartum depression- went to 10 mg no problem in 2008 -
May 2014 10 mg alternating days 7.25 mg- July 2014 7.25 every day
September 2014 7.25 alternating days 5 mg- November 2014 5 mg day
January 1 2015 back up to 10 mg - April 23, 2015 15mg
May 13, 2015 20mg - (tabs weight 25.0mg) February 26th 7.5mg off 25mg tablet
Sept 4th 2015 2.5 off 25mg tablet | March 18th. 8mg off 25mg tablet
October 30th. 3.5 off 25mg tablet. | April 11th. 9mg off 25mg tablet
November15th 4mg off 25mg tablet. | May 5th. 10mg off 25mg tablet
December 12th 5mg off 25 mg tablet | May 19th. 11mg off 25mg tablet
January 4 6mg off 25mg tablet |. June 7. 11.5 mg off 25mg tablet
January 25th. 6.5 off 25 mg tablet. July 11. 12 mg off 25 mg tablet
February 15th. 7mg off 25mg tablet. August 7 back down----October 13 2016 - omega 3 4800 mg per day - October 13, 2016--- vitamin d 4000mg per day

#2 nz11

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Posted 17 August 2016 - 09:57 PM

Thanks for posting that Vonnegutjunky,

 

I notice they quoted a study by  Rosenbaum in 1998 -ref 17, it was one in which he was paid a lot of money by Lilly to discredit prozacs competitiors who were threatening to overtake prozac sales.

That study has been highly criticized it was a Lilly sponsored study totally biased in prozac's favour.

 

Patients should be warned about these symptoms and the clinician should be aware of their potential to emerge.


2000 amitryptaline, nortriptaline venlafaxine clonazepam for  arm pain from keyboard use, told I had a chemical imbalance it would fix my arm was just a matter of finding the right med for me not informed of the nature of these drugs assured safe and not addictive, CT off Effexor after being told to double the dose on reporting adverse effects...later ..uncharacteristic psych panic tearful presented to doctor to get answers. Given paroxetine no questions asked 'safe and not addictive' next please.2001-2010 paroxetine (paxil) 2 failed attempts to quit, a learned helplessness set in. Feb 10 - Sept 10,  8 month clueless taper, hell. Doc said I had underlying depression .. I said that's not right' then found online support group and the truth!...overcome with inconceivable humiliation and outrage. 28 Sept 10 drug free ...  daily psych and emotional torture beginning in the waking hours of the morning receding somewhat in the evening only to start up again the next day. 28 Sept 12 (24 months) Stabilizing  (What an indescribable unimaginable non-functional nightmare). sleep issues start up at 3 yrs  waking daily at 2am -4.30am), April 2016 return to sport for the first time since drug free, Sept 16 return to work on casual basis.  28 Sept 16 (6yrs drug free), still cant sleep with any regularity, pssd continues no sign of improvement, still feel Rip van Winkle-ish, brain fog still improving, psoriasis concerns.

 

"It is unsafe for people who suffer from something that could be treated with an ssri to consult a psychiatrist." Gotzshe 2015. [ I think Gotzsche could have easily meant to say 'to consult anyone with prescribing privileges']. "Going to a psychiatrist is one of the most dangerous actions a person can take." Breggin

 

“Paroxetine is not safe, it is not effective and it meets every known definition of addictive.” McLaren, N, (2016) 'Psychiatry as bullsh*t’ p55..."Psychiatry is stuffed full of 'deep nonsense' better known as bullsh*t." McLaren 2016

 

"Within the first week of when you go on an antidepressant you may have a sexual dysfunction, it can go on forever, often only appearing when you go off the drug ...its extraordinarily common" Healy 2015

 

See  my intro post #451 for the xanax back story and for a CV -GSKs.  Come on guys get taperwise see a TaperMe Schedule

 For a staggeringly shocking 'prozac back story' see the truth post #523

 

"If I were an enemy combatant and the NZ army did this to me someone would be dragged to the Hague and jailed!"  nz11


#3 westcoast

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Posted 13 September 2016 - 05:29 PM

"Meta-analyses looking at gradual versus abrupt discontinuation failed to reliably demonstrate reduction of withdrawal symptoms with gradual reduction. "


2009: Cancer hospital said I had adjustment disorder because I thought they were doing it wrong. Their headshrinker prescribed Effexor, and my life set on a new course. I didn't know what was ahead, like a passenger on Disneyland's Matterhorn, smiling and waving as it climbs...clink, clink, clink.

2010: Post surgical accidental Effexor discontinuation by nurses, masked by intravenous Dilaudid. (The car is balanced at the top of the track.) I get home, pop a Vicodin, and ...

Whooosh...down, down, down, down, down...goes the trajectory of my life, up goes my mood and tendency to think everything is a good idea.
2012: After the bipolar jig was up, now a walking bag of unrelated symptoms, I went crazy on Daytrana (the Ritalin skin patch by Noven), because ADHD was a perfect fit for a bag of unrelated symptoms. I was prescribed Effexor for the nervousness of it, and things got neurological. An EEG showed enough activity to warrant an epilepsy diagnosis rather than non-epileptic ("psychogenic") seizures.

:o 2013-2014: Quit everything and got worse. I probably went through DAWS: dopamine agonist withdrawal syndrome. I drank to not feel, but I felt a lot: dread, fear, regret, grief: an utter sense of total loss of everything worth breathing about, for almost two years.

I was not suicidal but I wanted to be dead, at least dead to the experience of my own brain and body.

2015: I  began to recover after adding virgin coconut oil and organic grass-fed fed butter to a cup of instant coffee in the morning.

I did it hoping for mental acuity and better memory. After ten days of that, I was much better, mood-wise. Approximately neutral.

And, I experienced drowsiness. I could sleep. Not exactly happy, I did 30 days on Wellbutrin, because it had done me no harm in the past. 

I don't have the DAWS mood or state of mind. It never feel like doing anything if it means standing up.

In fact, I don't especially like moving. I'm a brain with a beanbag body.   :unsure:


#4 Altostrata

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Posted 13 September 2016 - 06:07 PM

The periods of "gradual reduction" were very short, tapering over a few weeks rather than a few days.


This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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#5 westcoast

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Posted 02 October 2016 - 12:49 PM

Do you know which meta-analyses they referred to? I don't see a reference that looks like a meta-analysis.


14. Mann AM MacPherson AS. Clinical experience with imipramine in the treatment of depression. Can Psych Assoc J. 1959 ; 4 : 38 - 47.

15. Blier P Tremblay P. Physiologic mechanisms underlying the antidepressant discontinuation syndrome. J Clin Psychiatry. 2006 ; 67 (Suppl 4): 8 - 13.

16. Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J Clin Psychiatry. 2006 ; 67 (Suppl 4): 14 - 21.

[This one was promising, but it's a review of the literature, not a meta-analysis]

17. Rosenbaum JF Fava M Hoog SL Ascroft RC Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998 ; 44 : 77 - 87. 10.1016/S0006-3223(98)00126-7

18. Haddad PM Anderson IM. Recognizing and managing antidepressant discontinuation symptoms. Adv Psychiatr Treat. 2007 ; 13 : 447 - 457. 10.1192/apt.bp.105.001966

[I think they relied heavily on Haddad and Anderson. I looks like they condensed all of the following into the short paragraph at the end of the antidepressants section that mentions mania and akathisia.
 

"Case reports have described a variety of reactions to discontinuation of antidepressants, including extra-pyramidal syndromes and mania/hypomania. The incidence of these syndromes is unknown, but the fact that they have not been observed in clinical studies suggests that they are uncommon.
--Sudden onset of mania/hypomania has been reported with termination of TCAs (e.g. Mirin et al, 1981), SSRIs (e.g. Szabadi, 1992; Bloch et al, 1995), MAOIs (e.g. Rothschild, 1985), venlafaxine (Goldstein et al, 1999) and mirtazapine (MacCall & Callender, 1999).
--[
Sudden onset of mania/hypomania] has been reported in patients with unipolar depression and bipolar disorder. 

--Parkinsonian symptoms have been reported following missed doses of desipramine (Dilsaver et al, 1983a), dystonia on stopping fluoxetine (Stoukides & Stoukides, 1991), and akathisia on stopping venlafaxine (Wolfe, 1997), fluvoxamine (Hirose, 2001) and imipramine (Sathananthan & Gershon, 1973).
--Various other discontinuation symptoms have occasionally been reported, but it is difficult to be sure that the relationship with drug termination is causal rather than a spurious association."

]


19. Black K Shea C Dursun S Kutcher S. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci. 2000 ; 25 : 255 - 261.

20. Fava GA Gatti A Belaise C Guidi J Offidani E. Withdrawal symptoms after SSRI discontinuation: a systematic review. Psychother Psychosom. 2015 ; 84 : 72 - 81. 10.1159/000370338
[The abstract for this one says "
Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering."]

21. Dilsaver SC Kronfol Z Sackellares JC Greden JF. Antidepressant withdrawal syndromes: evidence supporting the cholinergic overdrive hypothesis. J Clin Psychopharm. 1983 ; 3 : 157 - 164. 10.1097/00004714-198310000-00031

22. Gahr M Schonfeldt-Lecuona C Kolle MA Freudenmann RW. Withdrawal and discontinuation phenomena associated with tranylcypromine: a systematic review. Pharmacopsychiatry. 2013 ; 46 : 123 - 129. 10.1055/s-0032-1333265

23. Schatzberg AF Blier P Delgado PL Fava M Haddad PM Shelton RC. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry. 2006 ; 67 (Suppl 4): 27 - 30.


2009: Cancer hospital said I had adjustment disorder because I thought they were doing it wrong. Their headshrinker prescribed Effexor, and my life set on a new course. I didn't know what was ahead, like a passenger on Disneyland's Matterhorn, smiling and waving as it climbs...clink, clink, clink.

2010: Post surgical accidental Effexor discontinuation by nurses, masked by intravenous Dilaudid. (The car is balanced at the top of the track.) I get home, pop a Vicodin, and ...

Whooosh...down, down, down, down, down...goes the trajectory of my life, up goes my mood and tendency to think everything is a good idea.
2012: After the bipolar jig was up, now a walking bag of unrelated symptoms, I went crazy on Daytrana (the Ritalin skin patch by Noven), because ADHD was a perfect fit for a bag of unrelated symptoms. I was prescribed Effexor for the nervousness of it, and things got neurological. An EEG showed enough activity to warrant an epilepsy diagnosis rather than non-epileptic ("psychogenic") seizures.

:o 2013-2014: Quit everything and got worse. I probably went through DAWS: dopamine agonist withdrawal syndrome. I drank to not feel, but I felt a lot: dread, fear, regret, grief: an utter sense of total loss of everything worth breathing about, for almost two years.

I was not suicidal but I wanted to be dead, at least dead to the experience of my own brain and body.

2015: I  began to recover after adding virgin coconut oil and organic grass-fed fed butter to a cup of instant coffee in the morning.

I did it hoping for mental acuity and better memory. After ten days of that, I was much better, mood-wise. Approximately neutral.

And, I experienced drowsiness. I could sleep. Not exactly happy, I did 30 days on Wellbutrin, because it had done me no harm in the past. 

I don't have the DAWS mood or state of mind. It never feel like doing anything if it means standing up.

In fact, I don't especially like moving. I'm a brain with a beanbag body.   :unsure:


#6 Vonnegutjunky

Vonnegutjunky

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Posted 06 October 2016 - 09:47 PM

Sorry west
Coast - -I don't know -
Started 20mg Paxil 2006 due to postpartum depression- went to 10 mg no problem in 2008 -
May 2014 10 mg alternating days 7.25 mg- July 2014 7.25 every day
September 2014 7.25 alternating days 5 mg- November 2014 5 mg day
January 1 2015 back up to 10 mg - April 23, 2015 15mg
May 13, 2015 20mg - (tabs weight 25.0mg) February 26th 7.5mg off 25mg tablet
Sept 4th 2015 2.5 off 25mg tablet | March 18th. 8mg off 25mg tablet
October 30th. 3.5 off 25mg tablet. | April 11th. 9mg off 25mg tablet
November15th 4mg off 25mg tablet. | May 5th. 10mg off 25mg tablet
December 12th 5mg off 25 mg tablet | May 19th. 11mg off 25mg tablet
January 4 6mg off 25mg tablet |. June 7. 11.5 mg off 25mg tablet
January 25th. 6.5 off 25 mg tablet. July 11. 12 mg off 25 mg tablet
February 15th. 7mg off 25mg tablet. August 7 back down----October 13 2016 - omega 3 4800 mg per day - October 13, 2016--- vitamin d 4000mg per day