Tricyclic Plasma Research Articles

Amitriptyline dosage schedule, sampling time and tricyclic plasma levels.

SummaryPlasma levels of amitriptyline and nortriptyline were similar in ten depressed patients after administration of amitriptyline hydrochloride in three divided doses or as a single daily dose. Maximum comparability of the plasma levels is achieved by sampling 12 to 16 hours after the single daily dose, or 3 to 7 hours after the morning dose on a thrice-daily schedule. Owing to the long biological half-life of these drugs, therapeutic plasma levels are maintained on a once a day dosage schedule, and the need for sustained release preparations appears questionable.

Therapeutic monitoring of tricyclic antidepressants in plasma by gas chromatography.

We describe a comprehensive gas chromatographic analysis for therapeutic concentrations of amitriptyline, nortriptyline, imipramine, desipramine, doxepin, and desmethyldoxepin in plasma, with use of a nitrogen detector. All these drugs are extracted and chromatographed under identical conditions. Each tertiary amine tricyclic is well resolved from its secondary amine metabolite on a mixed-phase column and the concentrations of both are determined simultaneously, without derivatization. The lower limit of sensitivity is 10 microgram/liter of plasma (2-ml sample). Analytical recoveries of the tertiary and secondary amines are 100 and 80%, respectively. Between-run CV's for all of the drugs ranged between 5 and 7%.

Relationship between age and tricyclic antidepressant plasma levels.

Older depressed patients treated with imipramine or amitriptyline developed higher steady-state plasma levels of imipramine, desipramine, and amitriptyline. In imipramine-treated patients this finding was associated with a decreased rate of drug elimination from plasma. These findings provide at least a partial explanation for the increased susceptibility of the older patient to tricyclic antidepressant side effects and also provide a pharmacological rationale for use of lower dosages in this age group.

Simultaneous measurement of secondary and tertiary tricyclic antidepressants by GC/MS chemical ionization mass fragmentography.

We present a method for measuring seven commonly used tricyclic antidepressants in plasma. This method is suitable for monitoring therapeutic concentrations and for screening drug overdoses in cases where the identity of the abused tricyclic antidepressant may not be known. Drugs from alkalinized plasma are extracted into hexane in one step; two injections into the gas chromatograph/mass spectrometer follow. The tertiary amines (amitriptyline, doxepin, and imipramine) are analyzed by direct injection; the secondary amines (nortriptyline, desmethyldoxepin, desipramine, and protriptyline) are analyzed after derivitization with trifluoroacetic anhydride. Clomipramine and desmethyltrimipramine are suitable internal standards. Chemical ionization mass fragmentography, with methane as the reactant gas, is used. While maintaining specificity for these drugs, concentrations in human plasma ranging from 5 to 500 microng/liter can be measured. The coefficients of variation are about 4 to 11%.

Tricyclic Antidepressant Overdoses in Adolescent Patients

Tricyclic antidepressant plasma levels were measured in nine hospitalized adolescent oversdose patients to define the medical seriousness of the drug ingestion. Seven out of nine of these patients ingested medication prescribed for treatment of their psychiatric symptoms. Indications for tricyclic therapy in adolescents are vague. The more frequent use of these drugs makes the potential for life-threatening ingestions relatively common. The amount of drug ingested is usually poorly documented. Plasma measurements are of value in assessing the efficacy of the various medical treatments of overdose patients. Two of these nine overdoses were medically serious as defined by plasma measurements. Supportive care with cardiac monitoring was adequate in one case; however, a fatality occurred in the other under what could be described as optimal patient management conditions.

Tricyclic antidepressant plasma levels and adverse effects after overdose.

Forty patients ingesting tricyclic antidepressant (TAD) overdoses were studied as a pharmacologic model to determine whether total tricyclic antidepressant plasma levels correlated with major adverse effects and electrocardiographic findings. Maximum TAD plasma levels were higher in patients who died (p less than 0.025) or had cardiac arrest (p less than 0.02), needed respiratory support (p less than 0.005), were unconscious (p less than 0.02), had grand mal seizures (p less than 0.001), ventricular rate larger than or equal to 120/min (p less than 0.01), cardiac arrhythmia (p less than 0.05), QRS duration larger than or equal to 100 msec (p less than 0.001), or bundle branch block (p less than 0.05). TAD plasma levels correlated with the dose ingested by history (N = 29, r = 0.58, p less than 0.001). Measurement of total TAD (free and protein-bound) appears to correlate well with biologic response.

Therapeutic implications of tricyclic antidepressant plasma levels.

Methodological advances in drug assay techniques and their increasing availability have made the measurement of tricyclic antidepressant plasma levels more frequent and even fashionable. Plasma levels of tricyclics have been correlated with diagnosis, prognosis, clinical response, and side effects. But even in the area most extensively examined, the correlation between plasma level and clinical response, the results have been conflicting. Different studies have suggested that there is no relationship between plasma level and clinical response, as well as positive and negative correlations, and even a curvilinear relationship. On the basis of available evidence, it is impossible to define a therapeutic range of plasma levels that will be applicable to depressed patients as a group. For the moment, the problem of finding a suitable therapeutic dose for the individual patient remains of paramount importance. Studies to date suggest the need to take into consideration genetic factors, previous and present use of other drugs, the possibility that therapeutic failure might be a result of too high as well as too low a dose, as well as the possible relationship between high plasma levels and side effects. Also, since for the specific individual, the metabolism of different tricyclic antidepressants is similar, it may be useful to adjust dosages until a therapeutic one is obtained instead of immediately switching to another medication. Finally, although the usefulness of routine plasma level determination remains to be established, this technique may be indicated in cases of intractable depression and remains an important research tool.

Depressive Disorder in Childhood

Back to table of contents Previous article Next article ArticleNo AccessDepressive Disorder in ChildhoodROGER A. BRUMBACKROGER A. BRUMBACKSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.133.4.455AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Depressive Disorder in Childhood." American Journal of Psychiatry, 133(4), p. 455 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byThe Rise and Fall of the Diagnosis of Psychoneurosis of Childhood8 April 2019 | Journal of Nervous & Mental Disease, Vol. 207, No. 9Neurologic Clinics, Vol. 11, No. 1Neurologic Clinics, Vol. 8, No. 3Dépression Majeure Chez L'Enfant: Validation du Syndrome et Traitement Pharmacologique1 February 1989 | The Canadian Journal of Psychiatry, Vol. 34, No. 1Depression, Learning Disability, and School Behavior Problems31 August 2016 | Psychological Reports, Vol. 64, No. 1Depression and Dexamethasone Suppression Testing in Children and Adolescents2 July 2016 | Journal of Child Neurology, Vol. 2, No. 1Antidepressant Treatment of Children: Clinical Relapse is Unrelated to Tricyclic Plasma Concentrations22 October 2016 | Perceptual and Motor Skills, Vol. 60, No. 3American Journal of Orthopsychiatry, Vol. 53, No. 2Cognitive Improvement Associated with Tricyclic Antidepressant Treatment of Childhood Major Depressive Illness19 October 2016 | Perceptual and Motor Skills, Vol. 53, No. 1Non-Specificity of Motor Hyperactivity as a Diagnostic Criterion7 October 2016 | Perceptual and Motor Skills, Vol. 52, No. 1Neuropsychological Study of Children during and after Remission of Endogenous Depressive Episodes31 August 2016 | Perceptual and Motor Skills, Vol. 50, No. 3_supplRelation of Intelligence to Childhood Depression in Children Referred to an Educational Diagnostic Center7 October 2016 | Perceptual and Motor Skills, Vol. 50, No. 1Use of Operational Criteria in an Office Practice for Diagnosis of Children Referred for Evaluation of Learning or Behavior Disorders22 October 2016 | Perceptual and Motor Skills, Vol. 49, No. 1 Volume 133Issue 4 April 1976Pages 455-455 Metrics PDF download History Published online 1 April 2006 Published in print 1 April 1976

Tricyclic antidepressant overdose: clinical presentation and plasma levels.

Fifteen patients were studied at 8- to 12-hr intervals during the first 24 hr after overdosing with tricyclic antidepressants, and subsequently followed daily for up to 144 hr. The severity of the overdose was determined by measuring the plasma tricyclic antidepressant level using gas chromatography-mass fragmentography. No correlation was found between total, tertiary, or desmethyl tricyclic antidepressant plasma levels and maximum heart rate, lowest blood pressure, degree of unconsciousness, or EKG changes involving the P-R interval or ST-T wave changes. There was a weak correlation between drug plasma level and maximum pupil size (r = 0.46; p less than 0.05) and a strong correlation between the duration of the QRS complex and tricyclic antidepressant plasma levels (r = 0.75; p less than 0.01). All patients with a total tricyclic antidepressant plasma level greater than or equal to 1,000 ng/ml had a QRS interval greater than or equal to 100 msec. As the total plasma tricyclic level fell, the duration of the QRS interval returned to normal. Thus, the duration of the QRS complex on the electrocardiogram appears to be the most reliable clinical sign for evaluating the seriousness of tricyclic antidepressant overdosage.

Sensitive method for the routine determination of tricyclic antidepressants in plasma using a specific nitrogen detector

The sensitivity of the alkali flame ionization detector to the tricyclic antidepressant drugs has been studied and limits of detection measured. A backflush system has been used to enable measurements in plasma extracts. A general method for the estimation of tricyclic plasma levels has been developed and exemplified by the measurement of imipramine at therapeutic levels.

MURDER BY ADOLESCENTS WITH OBSCURE MOTIVATION

Back to table of contents Previous article Next article ArticleNo AccessMURDER BY ADOLESCENTS WITH OBSCURE MOTIVATIONA. WARREN STEARNSA. WARREN STEARNSSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.114.4.303AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail PDFThis content is only available as a PDF. Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited ByJuvenile Homicide Offenders: Classifications/Typologies1 March 2020Youth Homicide: A Review of the Literature and a Blueprint for Action27 July 2016 | International Journal of Offender Therapy and Comparative Criminology, Vol. 47, No. 1Adolescent Murderers1 October 1991 | The Canadian Journal of Psychiatry, Vol. 36, No. 8Homicidal Adolescents: A Replication1 September 2016 | Psychological Reports, Vol. 67, No. 3_supplJournal of Clinical Psychology, Vol. 46, No. 4Psychological Reports, Vol. 67, No. 7Journal of the American Academy of Child & Adolescent Psychiatry, Vol. 27, No. 5American Journal of Orthopsychiatry, Vol. 57, No. 3More Positive Supreme Court Views on PsychiatryDANIEL J. KENNELLY1 April 2006 | American Journal of Psychiatry, Vol. 142, No. 3Rate of change in tricyclic plasma levels important1 April 2006 | American Journal of Psychiatry, Vol. 142, No. 3Three case reports of a single homicidal adolescent1 April 2006 | American Journal of Psychiatry, Vol. 142, No. 3More positive supreme court views on psychiatry23 January 2015 | American Journal of Psychiatry, Vol. 142, No. 3A Study of Juvenile Murderers of Family Members27 July 2016 | International Journal of Offender Therapy and Comparative Criminology, Vol. 28, No. 3Aggressive Behavior, Vol. 3, No. 3Journal of the American Academy of Child Psychiatry, Vol. 16, No. 2Violence as a Function of Age and Relationship with Special Reference to Matricide *26 April 2017 | Canadian Psychiatric Association Journal, Vol. 16, No. 1 Volume 114Issue 4 October 1957Pages 303-305 Metrics PDF download History Published online 1 April 2006 Published in print 1 October 1957